Pesticidally active fused bicyclic heteroaromatic compounds

ABSTRACT

Compounds of formula (I), wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, can be used as insecticides.

The present invention relates to pesticidally active, in particularinsecticidally active quinazoline compounds, to processes for theirpreparation, to compositions comprising those compounds, and to theiruse for controlling animal pests, including arthropods and in particularinsects or representatives of the order Acarina.

WO2017192385 describes certain heteroaryl-1,2,4-triazole andheteroaryl-tetrazole compounds for use for controlling ectoparasites inanimals (such as a mammal and a non-mammal animal).

There have now been found novel pesticidally active quinazoline andquinoline compounds.

The present invention accordingly relates, in a first aspect, to acompound of the formula I

wherein:

A₁, A₂ and A₃ are, independently from each other, N or CR_(Y);

A₄ and A₅ are, independently from each other, N or CR_(Y);

Q is

R₁ is hydrogen, C₁-C₆alkyl, C₁-C₆cyanoalkyl, aminocarbonylC₁-C₆alkyl,hydroxycarbonylC₁-C₆alkyl, C₁-C₆nitroalkyl, trimethylsilaneC₁-C₆alkyl,C₁-C₃alkoxy-C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl,C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₄cycloalkylC₁-C₂alkyl-,C₃-C₄cycloalkylC₁-C₂alkyl- wherein the C₃-C₄cycloalkyl group issubstituted with 1 or 2 halogen atoms, oxetan-3-yl-CH₂—,C₁-C₆alkylcarbonyl, C₁-C₆alkoxycarbonyl, phenyloxycarbonyl,benzyloxycarbonyl, benzyl or benzyl substituted with 1 to 3 substituentsindependently selected from halogen, C₁-C₆alkoxy and C₁-C₆haloalkyl;

R_(2a) and R_(2b) are each independently selected from hydrogen,C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃haloalkylsuflanyl, C₁-C₃alkoxy,C₁-C₃haloalkoxy, halogen, NO₂, SF₅, CN, C(O)NH₂, C(O)OH, C(S)NH₂,C₃-C₆cycloalkyl, C₃-C₆cycloalkyl substituted with one to threesubstituents independently selected from R_(x), C₃-C₆cycloalkylcarbonyl,phenyl, phenyl substituted with one to three substituents independentlyselected from R_(x), heteroaryl, heteroaryl substituted with one tothree substituents independently selected from R_(x), OR₆,piperidin-2-one-1-yl, piperidin-2-one-1-yl substituted with one to twosubstituents independently selected from R_(x), pyridin-2-one-1-yl,pyridin-2-one-1-yl substituted with one to two substituentsindependently selected from R_(x), azetidin-1-yl, azetidin-1-ylsubstituted with one to two substituents independently selected fromR_(x) pyrrolidin-1-yl, pyrrolidin-1-yl substituted with one to twosubstituents independently selected from R_(x),C₃-C₆cycloalkylC₁-C₄alkyl, C₃-C₆cycloalkylC₁-C₄alkyl substituted withone to two substituents independently selected from R_(z);C₃-C₆cycloalkylC₁-C₃alkoxy, C₃-C₆cycloalkylC₁-C₃alkoxy substituted withone to two substituents independently selected from R_(x),C₁-C₆cyanoalkyl, C₁-C₆cyanoalkoxy, C₁-C₄alkylsulfanyl,C₁-C₄alkylsulfanyl substituted with one to three substituentsindependently selected from R_(x), C₁-C₄alkylsulfonyl,C₁-C₄alkylsulfonyl substituted with one to three substituentsindependently selected from R_(x), C₁-C₄alkylsulfinyl, andC₁-C₄alkylsulfinyl substituted with one to three substituentsindependently selected from R_(x);

R₃ is C₁-C₃alkyl or C₁-C₃haloalkyl;

R₄ is pyridine, pyrimidine, pyrazine or pyridazine; or

R₄ is pyridine, pyrimidine, pyrazine or pyridazine each of which,independently of each other, is substituted with one to two substituentsindependently selected from C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,C₃-C₄cycloalkyl, halo, hydroxyl, CN, C₁-C₆haloalkoxy,C₂-C₆haloalkenyloxy, C₂-C₆haloalkynyloxy, C₃-C₄halocycloalkoxy.NH₂C(O)—, NH₂C(S)—, (OH)N═C(NH₂)— and a 5-membered heteroaryl ringoptionally substituted by 1 to 3 substituents independently selectedfrom halogen, C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy andC₁-C₃haloalkoxy;

R_(4a) is pyridine, pyrimidine, pyrazine, pyridazine; or

R_(4a) is pyridine, pyrimidine, pyrazine or pyridazine each of which,independently of each other, is substituted with one to threesubstituents independently selected from C₁-C₃alkyl, C₁-C₃haloalkyl,C₁-C₃alkoxy, C₃-C₄cycloalkyl, halogen, hydroxyl, cyano, andC₁-C₃haloalkoxy; or

R_(4a) is Y1, Y2, Y3, and Y4

wherein, R′_(4a), R′_(4b), and R′_(4c), independently of each other andindependently of Y1 to Y4, are selected from hydrogen, halogen, CN,C₁-C₃alkyl, C₁-C₃haloalkyl, C₃-C₄cycloalkyl, C₁-C₃alkoxy, andC₁-C₃haloalkoxy;

R₅ is hydrogen, C₁-C₃alkyl, C₁-C₃haloalkyl, C₃-C₄cycloalkyl,C₁-C₃alkoxy, C₃-C₄alkoxyC(O)—, (C₁-C₃alkoxy)₂CH—, halogen, CN, NH₂C(O),amino (i.e NH₂), (C₁-C₃alkyl)amino, di(C₁-C₃alkyl)amino, hydroxy,C₃-C₄halocycloalkyl, C₃-C₄cyanocycloalkyl, C₂-C₆alkenyl,C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl,C₁-C₄haloalkylsulfanyl, C₁-C₄haloalkylsulfinyl, C₁-C₄haloalkylsulfonyl,C₁-C₄alkylsulfanyl, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl,C₁-C₃alkoxy-C₁-C₃alkyl, C₁-C₃alkoxy-C₁-C₃alkoxy-C₁-C₃alkyl,(C₁-C₃alkyl)sulfonylamino, (C₁-C₃alkyl)sulfonyl(C₁-C₃alkyl)amino,(C₁-C₃alkyl)NHC(O), (C₁-C₃alkyl)₂NC(O), (C₁-C₃cycloalkyl)NHC(O),(C₁-C₃cycloalkyl)(C₁-C₃alkyl)NC(O), (C₁-C₃alkyl)C(O)(C₁-C₃alkyl)N,(C₁-C₃alkyl)C(O)NH, (C₁-C₃alkyl)C(O), (C₁-C₃alkoxy)C(O), HC(O),diphenylmethanimine, C₁-C₃haloalkoxy, phenyl, or a 5-memberedheteroaromatic ring; or

R₅ is phenyl substituted with one to three substituents selected fromC₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₃-C₄cycloalkyl, halogen, CNand hydroxyl; or

R₅ is a 5-membered heteroaromatic ring substituted with one to threesubstituents selected from C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,C₃-C₄cycloalkyl, halogen, CN and hydroxyl;

R_(5a) and R_(5b) are, independently of each other, selected fromhydrogen, halogen, CN, C₁-C₃alkyl, C₁-C₃haloalkyl, C₃-C₄cycloalkyl,C₁-C₃alkoxy, and C₁-C₃haloalkoxy;

R₆ is phenyl, benzyl, heteroaryl, or C₃-C₆ cycloalkyl; or

R₆ is phenyl, benzyl, heteroaryl, or C₃-C₆ cycloalkyl, each of which,independent of each other, is substituted with one to three substituentsindependently selected from R_(x);

R_(x) is independently selected from halogen, C₁-C₃alkyl,C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, NO₂, SF₅, CN, C(O)NH₂,C(S)NH₂, C₁-C₄haloalkylsulfanyl, C₁-C₄haloalkylsulfinyl,C₁-C₄haloalkylsulfonyl, C₁-C₄alkylsulfanyl, C₁-C₄alkylsulfinyl andC₁-C₄alkylsulfonyl;

R_(Y) is selected from hydrogen, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃alkoxy, C₁-C₃ haloalkoxy, halogen, CN and cyclopropyl; and

R_(Z) is selected from oxo, halogen, C₁-C₃ alkyl, C₁-C₃haloalkyl,C₁-C₃alkoxy, C₁-C₃haloalkoxy and CN;

or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomerand N-oxide of the compound of formula I.

Compounds of formula I which have at least one basic centre can form,for example, acid addition salts, for example with strong inorganicacids such as mineral acids, for example perchloric acid, sulfuric acid,nitric acid, nitrous acid, a phosphorus acid or a hydrohalic acid, withstrong organic carboxylic acids, such as C₁-C₄alkanecarboxylic acidswhich are unsubstituted or substituted, for example by halogen, forexample acetic acid, such as saturated or unsaturated dicarboxylicacids, for example oxalic acid, malonic acid, succinic acid, maleicacid, fumaric acid or phthalic acid, such as hydroxycarboxylic acids,for example ascorbic acid, lactic acid, malic acid, tartaric acid orcitric acid, or such as benzoic acid, or with organic sulfonic acids,such as C₁-C₄alkane- or arylsulfonic acids which are unsubstituted orsubstituted, for example by halogen, for example methane- orp-toluenesulfonic acid. Compounds of formula I which have at least oneacidic group can form, for example, salts with bases, for examplemineral salts such as alkali metal or alkaline earth metal salts, forexample sodium, potassium or magnesium salts, or salts with ammonia oran organic amine, such as morpholine, piperidine, pyrrolidine, a mono-,di- or tri-lower-alkylamine, for example ethyl-, diethyl-, triethyl- ordimethylpropylamine, or a mono-, di- or trihydroxy-lower-alkylamine, forexample mono-, di- or triethanolamine.

In each case, the compounds of formula I according to the invention arein free form, in oxidized form as a N-oxide or in salt form, e.g. anagronomically usable salt form.

N-oxides are oxidized forms of tertiary amines or oxidized forms ofnitrogen containing heteroaromatic compounds. They are described forinstance in the book “Heterocyclic N-oxides” by A. Albini and S. Pietra,CRC Press, Boca Raton 1991.

The compounds of formula I according to the invention also includehydrates which may be formed during the salt formation.

The term “C₁-C_(n)alkyl” as used herein refers to a saturatedstraight-chain or branched hydrocarbon radical attached via any of thecarbon atoms having 1 to n carbon atoms, for example, any one of theradicals methyl, ethyl, n-propyl, 1-methylbutyl, 2-methylbutyl,3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, n-pentyl,1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl,3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl,1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl,3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl,1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, or1-ethyl-2-methylpropyl.

The term “C₁-C_(n)haloalkyl” as used herein refers to a straight-chainor branched saturated alkyl radical attached via any of the carbon atomshaving 1 to n carbon atoms (as mentioned above), where some or all ofthe hydrogen atoms in these radicals may be replaced by fluorine,chlorine, bromine and/or iodine, i.e., for example, any one ofchloromethyl, dichloromethyl, trichloromethyl, fluoromethyl,difluoromethyl, trifluoromethyl, chlorofluoromethyl,dichlorofluoromethyl, chlorodifluoromethyl, 2-fluoroethyl,2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl,2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl,2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl,2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl,2,2-difluoropropyl, 2,3-difluoropropyl, 2-chloropropyl, 3-chloropropyl,2,3-dichloropropyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl,3,3,3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl,1-(fluoromethyl)-2-fluoroethyl, 1-(chloromethyl)-2-chloroethyl,1-(bromomethyl)-2-bromoethyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutylor nonafluorobutyl. According a term “C₁-C₂fluoroalkyl” would refer to aC₁-C₂alkyl radical which carries 1, 2, 3, 4, or 5 fluorine atoms, forexample, any one of difluoromethyl, trifluoromethyl, 1-fluoroethyl,2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl,1,1,2,2-tetrafluoroethyl or pentafluoroethyl.

The term “C₁-C_(n)alkoxy” as used herein refers to a straight-chain orbranched saturated alkyl radical having 1 to n carbon atoms (asmentioned above) which is attached via an oxygen atom, i.e., forexample, any one of the radicals methoxy, ethoxy, n-propoxy,1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy or1,1-dimethylethoxy. The term “haloC₁-C_(n)alkoxy” as used herein refersto a C₁-C_(n)alkoxy radical where one or more hydrogen atoms on thealkyl radical is replaced by the same or different halo atom(s)—examplesinclude trifluoromethoxy, 2-fluoroethoxy, 3-fluoropropoxy,3,3,3-trifluoropropoxy, 4-chlorobutoxy.

The term “C₁-C_(n)cyanoalkyl” as used herein refers to a straight chainor branched saturated C₁-C_(n)alkyl radical having 1 to n carbon atoms(as mentioned above), where one of the hydrogen atoms in these radicalsis be replaced by a cyano group: for example, cyanomethyl, 2-cyanoethyl,2-cyanopropyl, 3-cyanopropyl, 1-(cyanomethyl)-2-ethyl,1-(methyl)-2-cyanoethyl, 4-cyanobutyl, and the like.

The term “C₃-C_(n)cycloalkyl” as used herein refers to 3-n memberedcycloalkyl groups such as cyclopropane, cyclobutane, cyclopentane andcyclohexane.

The term “C₃-C_(n)cycloalkylcarbonyl” as used herein refers to a 3-nmembered cycloalkyl group attached to a carbonyl (C═O) group, whichcarbonyl group is connected to the rest of the molecule.

Similarly the terms “C₁-C_(n)alkylcarbonyl”, “C₁-C_(n)alkoxycarbonyl”,“phenyloxycarbonyl” and “benzyloxycarbonyl” as used herein refers to analkyl, alkoxy, phenyloxy and benzyloxy group attached to a carbonyl(C═O) group, which carbonyl group is connected to the rest of themolecule.

The term “C₃-C₄cycloalkyl-C₁-C₂alkyl” as used herein refers to 3 or 4membered cycloalkyl group with either a methylene or ethylene group,which methylene or ethylene group is connected to the rest of themolecule. In the instance, the C₃-C₄cycloalkyl-C₁-C₂alkyl- group issubstituted, the substituent(s) can be on the cycloalkyl group and/or onthe alkyl group.

The term “C₃-C₆cycloalkylC₁-C₄haloalkoxy” as used herein refers to a 3to 6 membered cycloalkyl group connected to a 1 to 4 memberedhaloalkoxy, which haloalkoxy group is connected to the rest of themolecule.

The term “aminocarbonylC₁-C_(n)alkyl” as used herein refers to an alkylradical where one of the hydrogen atoms in the radical is replaced byCONH2 group.

The term “hydroxycarbonylC₁-C_(n)alkyl” as used herein refers to analkyl radical where one of the hydrogen atoms in the radical is replacedby COOH group.

The term “C₁-C_(n)alkylsulfanyl” as used herein refers to aC₁-C_(n)alkyl moiety linked through a sulfur atom. Similarly, the term“C₁-C_(n)haloalkylthio” or “C₁-C_(n)haloalkylsulfanyl” as used hereinrefers to a C₁-Cohaloalkyl moiety linked through a sulfur atom.Similarly, the term “C₃-C_(n)cycloalkylsulfanyl” refers to 3-n memberedcycloalkyl moiety linked through a sulfur atom.

The term “C₁-C_(n)alkylsulfinyl” as used herein refers to aC₁-C_(n)alkyl moiety linked through the sulfur atom of the S(═O) group.Similarly, the term “C₁-C_(n)haloalkylsulfinyl” or“C₁-C_(n)haloalkylsulfinyl” as used herein refers to a C₁-C_(n)haloalkylmoiety linked through the sulfur atom of the S(═O) group.

Similarly, the term “C₃-C_(n)cycloalkylsulfinyl” refers to 3-n memberedcycloalkyl moiety linked through the sulfur atom of the S(═O) group.

The term “C₁-C_(n)alkylsulfonyl” as used herein refers to aC₁-C_(n)alkyl moiety linked through the sulfur atom of the S(═O)₂ group.Similarly, the term “C₁-C_(n)haloalkylsulfonyl” or“C₁-C_(n)haloalkylsulfonyl” as used herein refers to a C₁-C_(n)haloalkylmoiety linked through the sulfur atom of the S(═O)₂ group.

Similarly, the term “C₃-C_(n)cycloalkylsulfonyl” refers to 3-n memberedcycloalkyl moiety linked through the sulfur atom of the S(═O)₂ group

The term “trimethylsilaneC₁-C_(n)alkyl” as used herein refers to analkyl radical where one of the hydrogen atoms in the radical is replacedby a —Si(CH₃)₃ group.

The term “C₂-C_(n)alkenyl” as used herein refers to a straight orbranched alkenyl chain having from two to n carbon atoms and one or twodouble bonds, for example, ethenyl, prop-1-enyl, but-2-enyl.

The term “C₂-C_(n)haloalkenyl” as used herein refers to aC₂-C_(n)alkenyl moiety substituted with one or more halo atoms which maybe the same or different.

The term “C₂-C_(n)alkynyl” as used herein refers to a straight orbranched alkynyl chain having from two to n carbon atoms and one triplebond, for example, ethynyl, prop-2-ynyl, but-3-ynyl.

The term “C₂-C_(n)haloalkynyl” as used herein refers to aC₂-C_(n)alkynyl moiety substituted with one or more halo atoms which maybe the same or different.

Halogen or “halo” is generally fluorine, chlorine, bromine or iodine.This also applies, correspondingly, to halogen in combination with othermeanings, such as haloalkyl

The term “heteroaryl” as used herein refers to a 5- or 6-memberedaromatic monocyclic ring having 1 to 3 heteroatoms independentlyselected from N, O and S. Examples are heteroaryls J-1 to J-35 shown inScheme A below. Preferred heteroaryl preferred is pyridyl, pyrimidyl,and pyrazolyl.

The pyridine, pyrimidine, pyrazine and pyridazine groups (unsubstitutedor substituted) for R₄ and R_(4a) are each connected via a carbon atomon the respective ring to the rest of the compound.

As used herein, the term “controlling” refers to reducing the number ofpests, eliminating pests and/or preventing further pest damage such thatdamage to a plant or to a plant derived product is reduced.

The staggered line as used herein, for example, in Q^(a) and Y-1,represent the point of connection/attachment to the rest of thecompound.

As used herein, the term “pest” refers to insects, and molluscs that arefound in agriculture, horticulture, forestry, the storage of products ofvegetable origin (such as fruit, grain and timber); and those pestsassociated with the damage of man-made structures. The term pestencompasses all stages in the life cycle of the pest.

As used herein, the term “effective amount” refers to the amount of thecompound, or a salt thereof, which, upon single or multiple applicationsprovides the desired effect.

An effective amount is readily determined by the skilled person in theart, by the use of known techniques and by observing results obtainedunder analogous circumstances. In determining the effective amount anumber of factors are considered including, but not limited to: the typeof plant or derived product to be applied; the pest to be controlled &its lifecycle; the particular compound applied; the type of application;and other relevant circumstances.

As one of ordinary skill in the art will appreciate, compounds offormula I contain a stereogenic centre which is indicated with anasterisk in the structure below:

where R₁, R_(2a), R_(2b), R₃, Q, A₁, A₂, A₃, A₄, and A₅ are as definedin the first aspect.

The present invention contemplates both racemates and individualenantiomers. Compounds having preferred stereochemistry are set outbelow.

Particularly preferred compounds of the present invention are compoundsof formula I′a:

where R₁, R_(2a), R_(2b), R₃, Q, A₁, A₂, A₃, A₄, and A₅ are as definedin the first aspect, and stereoisomers, enantiomers, tautomers andN-oxides of the compounds of formula (I′a), and agrochemicallyacceptable salts thereof.

The term “optionally substituted” as used herein means that the groupreferenced is either unsubstituted or is substituted by a designatedsubstituent, for example, “C₃-C₄cycloalkyl is optionally substitutedwith 1 or 2 halo atoms” means C₃-C₄cycloalkyl, C₃-C₄cycloalkylsubstituted with 1 halo atom and C₃-C₄cycloalkyl substituted with 2 haloatoms.

Embodiments according to the invention are provided as set out below.

In an embodiment of each aspect of the invention,

-   -   A. A₁, A₂ and A₃ are, independently from each other, N or        CR_(Y), with the proviso that no more than two out of the three        are N; or    -   B. A₁ and A₃ are N and A₂ is CR_(Y); or    -   C. A₁, A₂ and A₃ are, independently from each other, N or CH; or    -   D. A₁, A₂ and A₃ are, independently from each other, N or CH,        with the proviso that no more than two out of the three are N;        or    -   E. A₁ is N, and A₂ and A₃ are CH; or    -   F. A₁ and A₂ CH, and A₃ is N; or    -   G. A₁ and A₃ are N, and A₂ is CH; or    -   H. A₁ and A₃ are N, and A₂ is CH.

In an embodiment of each aspect of the invention,

-   -   A. A₄ is CR_(Y), and A₅ is N; or    -   B. A₄ is CR_(Y), and A₅ is CH; or    -   C. A₄ is CH, and A₅ is N; or    -   D. A₄ is N, and A₅ is CH; or    -   E. A₄ and A₅ are both CH.

In an embodiment of each aspect of the invention,

-   -   A. A₁ is N, A₂ and A₃ are CH, and A₄ and A₅ are both CH; or    -   B. A₁ and A₂ are CH, A₃ is N, and A₄ and A₅ are both CH.    -   C. A₁ and A₃ are N, A₂ is CH, and A₄ is CRY and A₅ is CH; or    -   D. A₁ and A₃ are N, A₂ is CH, and A₄ is CH and A₅ is N; or    -   E. A₁ and A₃ are N, A₂ is CH, and A₄ is N and A₅ is CH; or    -   F. A₁ and A₃ are N, A₂ is CH, and A₄ is N or CH and A₅ is CH; or    -   G. A₁ and A₃ are N, A₂ is CH, and A₄ is CH and A₅ is N or CH; or    -   H. A₁ and A₃ are N, A₂ is CH, and A₄ and A₅ are both N; or    -   I. A₁ and A₃ are N, A₂ is CH, and A₄ and A₅ are both CH.

In an embodiment of each aspect of the invention, R₁ is

-   -   A. hydrogen, C₁-C₆alkyl, C₁-C₆cyanoalkyl,        aminocarbonylC₁-C₆alkyl, hydroxycarbonylC₁-C₆alkyl,        C₁-C₆nitroalkyl, trimethylsilaneC₁-C₆alkyl,        C₁-C₃alkoxy-C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl,        C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl,        C₃-C₄cycloalkylC₁-C₂alkyl-, C₃-C₄cycloalkylC₁-C₂alkyl- wherein        the C₃-C₄cycloalkyl group is substituted with 1 or 2 halogen        atoms, oxetan-3-yl-CH₂—, C₁-C₃alkylcarbonyl,        C₁-C₃alkoxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, or        benzyl; or    -   B. hydrogen, C₁-C₆alkyl, C₁-C₆cyanoalkyl,        aminocarbonylC₁-C₆alkyl, hydroxycarbonylC₁-C₆alkyl,        C₁-C₆nitroalkyl, trimethylsilaneC₁-C₆alkyl,        C₁-C₃alkoxy-C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl,        C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl,        C₃-C₄cycloalkylC₁-C₂alkyl-, benzyloxycarbonyl, or benzyl; or    -   C. hydrogen, C₁-C₆alkyl, C₁-C₆cyanoalkyl,        aminocarbonylC₁-C₆alkyl, hydroxycarbonylC₁-C₆alkyl,        C₁-C₃alkoxy-C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl,        C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl,        C₃-C₄cycloalkylC₁-C₂alkyl-, benzyloxycarbonyl, or benzyl; or    -   D. hydrogen, C₁-C₆alkyl, C₁-C₆cyanoalkyl,        C₁-C₃alkoxy-C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl,        C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl,        C₃-C₄cycloalkylC₁-C₂alkyl-, benzyloxycarbonyl, or benzyl; or    -   E. hydrogen, C₁-C₃alkyl, C₁-C₃cyanoalkyl,        C₁-C₃alkoxy-C₁-C₃alkyl, C₁-C₃haloalkyl, C₂-C₄alkenyl,        C₂-C₄haloalkenyl, C₂-C₄alkynyl, C₂-C₄haloalkynyl,        C₃-C₄cycloalkylC₁-C₂alkyl-, benzyloxycarbonyl, or benzyl; or    -   F. hydrogen, C₁-C₃alkyl, C₁-C₃cyanoalkyl,        C₁-C₃alkoxy-C₁-C₃alkyl, C₁-C₃haloalkyl, C₂-C₄alkenyl,        C₂-C₄haloalkenyl, C₂-C₄alkynyl, C₂-C₄haloalkynyl,        C₃-C₄cycloalkylC₁-C₂alkyl-, benzyloxycarbonyl, or benzyl; or    -   G. hydrogen, methyl, ethyl, cyanomethyl, methoxymethyl,        cyclopropyl-methyl, allyl, propargyl, benzyloxycarbonyl, or        benzyl; or    -   H. hydrogen, methyl, ethyl, allyl, propargyl or        cyclopropyl-methyl; or    -   I. hydrogen, methyl, propargyl or cyclopropyl-methyl;

In an embodiment of each aspect of the invention, R_(2a) is

-   -   A. hydrogen, halogen, C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,        C₁-C₃haloalkoxy, CN, C₃-C₄cycloalkyl, C₃-C₆cycloalkylcarbonyl,        phenyl, heteroaryl selected from J-1 and J-35, each of        C₃-C₄cycloalkyl, phenyl or heteroaryl, independent of each        other, is substituted with one to three substituents R_(x), OR₆,        piperidin-2-one-1-yl, pyridin-2-one-1-yl, azetidin-1-yl        optionally substituted with R_(x), pyrrolidin-1-yl,        C₃-C₆cycloalkylC₁-C₄alkyl substituted with one or two        substituents R_(Z), C₃-C₆cycloalkylC₁-C₃alkoxy optionally        substituted with R_(x), C₁-C₆cyanoalkyl, C₁-C₆cyanoalkoxy,        C₁-C₄alkylsulfanyl optionally substituted by one to three        substituents R_(x), C₁-C₄alkylsulfonyl optionally substituted by        one to three substituents R_(x), or C₁-C₄alkylsulfinyl        optionally substituted by one to three substituents R_(x); or    -   B. hydrogen, halogen, C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,        C₁-C₃haloalkoxy, CN, C₃-C₄cycloalkyl, C₃-C₆cycloalkylcarbonyl,        phenyl, pyrazolyl, each of C₃-C₄cycloalkyl, phenyl, pyrazolyl,        independent of each other, is substituted with one to three        substituents R_(x), OR₆, piperidin-2-one-1-yl,        pyridin-2-one-1-yl, azetidin-1-yl optionally substituted with        R_(x), pyrrolidin-1-yl, C₃-C₆cycloalkylC₁-C₄alkyl optionally        substituted with one or two substituents R_(Z),        C₃-C₆cycloalkylC₁-C₃alkoxy optionally substituted with R_(x),        C₁-C₆cyanoalkyl, C₁-C₆cyanoalkoxy, C₁-C₄alkylsulfanyl optionally        substituted by one to three substituents R_(x),        C₁-C₄alkylsulfonyl optionally substituted by one to three        substituents R_(x), or C₁-C₄alkylsulfinyl optionally substituted        by one to three substituents R_(x); or    -   C. hydrogen, halogen, C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,        C₁-C₃haloalkoxy, CN, C₃-C₄cycloalkyl, C₃-C₆cycloalkylcarbonyl,        phenyl or pyrazolyl, each of C₃-C₄cycloalkyl, phenyl, pyrazolyl,        independent of each other, is substituted with one to two        substituents R_(x), OR₆, azetidin-1-yl optionally substituted        with R_(x), C₃-C₆cycloalkylC₁-C₄alkyl optionally substituted        with one or two substituents R_(Z), C₃-C₆cycloalkylC₁-C₃alkoxy        optionally substituted with R_(x), C₁-C₄alkylsulfanyl optionally        substituted by one to three substituents R_(x),        C₁-C₄alkylsulfonyl optionally substituted by one to three        substituents R_(x), or C₁-C₄alkylsulfinyl optionally substituted        by one to three substituents R_(x); or    -   D. hydrogen, halogen, C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,        C₁-C₃haloalkoxy, CN, C₃-C₄cycloalkyl, C₃-C₄cycloalkyl        substituted with one to two substituents R_(x),        C₃-C₆cycloalkylcarbonyl, OR₆, C₃-C₆cycloalkylC₁-C₄alkyl,        C₃-C₆cycloalkylC₁-C₄alkyl substituted with one or two        substituents R_(Z), C₁-C₄alkylsulfanyl, C₁-C₄alkylsulfanyl        substituted by one to three substituents R_(x),        C₁-C₄alkylsulfonyl, C₁-C₄alkylsulfonyl substituted by one to        three substituents R_(x), C₁-C₄alkylsulfinyl, or        C₁-C₄alkylsulfinyl substituted by one to three substituents        R_(x); or    -   E. hydrogen, halogen, C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,        C₁-C₃haloalkoxy, CN, C₃-C₄cycloalkyl, C₃-C₄cycloalkyl        substituted with one to two substituents independently selected        from halogen, C₁-C₃alkyl and C₁-C₃haloalkyl,        C₃-C₄cycloalkylcarbonyl, C₃-C₄cycloalkylmethyl,        C₃-C₄cycloalkylmethyl substituted with one to two substituents        independently selected from oxo, halogen, C₁-C₃alkyl, and        C₁-C₃haloalkyl, C₁-C₂alkylsulfanyl substituted with one to three        halogens or C₁-C₂alkylsulfonyl substituted with one to three        halogens; or    -   F. hydrogen, halogen, C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,        C₁-C₃haloalkoxy, cyclopropyl, cyclopropyl substituted with one        to two substituents independently selected from halogen, methyl,        and trifluoromethyl, cyclopropylcarbonyl, cyclopropylmethyl        substituted with one to two substituents independently selected        from oxo, halogen, and trifluomethyl, or C₁-C₂alkylsulfanyl        substituted with one to three halogens or C₁-C₂alkylsulfonyl        substituted with one to three halogens; or    -   G. hydrogen, halogen, C₁-C₃alkyl, C₁-C₃haloalkyl,        C₁-C₃haloalkylsulfanyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, CN,        C₃-C₆cycloalkyl, C₃-C₆cycloalkyl substituted with one to three        substituents independently selected from C₁-C₃alkyl,        C₁-C₃haloalkyl, cyano, and halogen, cyclopropylcarbonyl,        C₃-C₆cycloalkylC₁-C₄alkyl, C₃-C₆cycloalkylC₁-C₄alkyl substituted        with one to five substituents independently selected from oxo,        C₁-C₃alkyl, C₁-C₃haloalkyl, cyano, and halogen, C₁-C₆cyanoalkyl,        C₁-C₄alkylsulfonyl, C₁-C₄haloalkylsulfonyl, C₁-C₄alkylsulfinyl,        C₁-C₄haloalkylsulfinyl, C₃-C₆cycloalkylsulfanyl,        C₃-C₆cycloalkylsulfinyl, or C₃-C₆cycloalkylsulfonyl; or    -   H. hydrogen, halogen, C₁-C₃alkyl, C₁-C₃haloalkyl,        C₁-C₃haloalkylsulfanyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, CN,        C₃-C₆cycloalkyl, C₃-C₆cycloalkyl substituted with one or two        substituents independently selected from C₁-C₃haloalkyl, cyano,        and halogen, C₃-C₄cycloalkylcarbonyl, C₃-C₆cycloalkylC₁-C₄alkyl,        C₃-C₆cycloalkylC₁-C₄alkyl substituted with one to three        substituents independently selected from oxo, C₁-C₃haloalkyl,        cyano, and halogen, C₁-C₆cyanoalkyl, C₁-C₄alkylsulfonyl,        C₁-C₄haloalkylsulfonyl, C₁-C₄alkylsulfinyl,        C₁-C₄haloalkylsulfinyl, C₃-C₆cycloalkylsulfanyl,        C₃-C₆cycloalkylsulfinyl, or C₃-C₆cycloalkylsulfonyl; or    -   I. hydrogen, halogen, C₁-C₃haloalkyl, C₁-C₃haloalkylsulfanyl,        C₁-C₃haloalkoxy, C₃-C₆cycloalkyl, C₃-C₆cycloalkyl substituted        with one or two substituents independently selected from        C₁-C₃haloalkyl, cyano, and halogen, C₃-C₄cycloalkylcarbonyl,        C₃-C₆cycloalkylC₁-C₄alkyl, C₃-C₆cycloalkylC₁-C₄alkyl substituted        with one to three substituents independently selected from oxo,        C₁-C₃haloalkyl, cyano, and halogen, C₁-C₆cyanoalkyl,        C₁-C₄alkylsulfonyl, C₁-C₄haloalkylsulfonyl, C₁-C₄alkylsulfinyl,        C₁-C₄haloalkylsulfinyl, C₃-C₆cycloalkylsulfanyl,        C₃-C₆cycloalkylsulfinyl, or C₃-C₆cycloalkylsulfonyl; or    -   J. hydrogen, halogen, C₃-C₄cycloalkyl, C₃-C₄cycloalkylcarbonyl,        C₃-C₄cycloalkyl-C₁-C₂alkyl optionally substituted with one to        two substituents selected from oxo, halogen, C₁-C₃alkyl and        C₁-C₃haloalkyl, C₁-C₃haloalkyl, C₁-C₃haloalkylsulfanyl,        C₁-C₃haloalkysulfonyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, or CN; or    -   K. halogen, C₁-C₃haloalkyl, C₁-C₃haloalkylsulfanyl,        C₁-C₃haloalkysulfonyl, or C₁-C₃haloalkoxy; or    -   L. halogen, C₁-C₂haloalkyl, C₁-C₂haloalkylsulfanyl,        C₁-C₂haloalkysulfonyl, or C₁-C₂haloalkoxy; or    -   M. chlorine, fluorine, bromine, iodine, difluoromethyl,        trifluoromethyl, trifluoromethylsulfanyl or        trifluoromethylsulfonyl; or    -   N. fluorine, chlorine, bromine, iodine, trifluoromethylsulfanyl,        trifluoromethylsulfonyl or trifluoromethyl; or    -   O. trifluoromethyl, fluorine, bromine or chlorine.

In an embodiment of each aspect of the invention, R_(2b) is

-   -   A. hydrogen, halogen, C₁-C₃alkyl, C₁-C₃haloalkyl,        C₃-C₄cycloalkyl, cyclopropylcarbonyl, C₃-C₆cycloalkylC₁-C₄alkyl        optionally substituted with one or two substituents R_(Z),        C₁-C₃alkoxy, C₁-C₃haloalkoxy, or CN, C₁-C₄alkylsulfanyl        optionally substituted by one to three substituents R_(x),        C₁-C₄alkylsulfonyl optionally substituted by one to three        substituents R_(x), or C₁-C₄alkylsulfinyl optionally substituted        by one to three substituents R_(x); or    -   B. hydrogen, halogen, C₃-C₄cycloalkyl, cyclopropylcarbonyl,        C₃-C₄cycloalkyl-C₁-C₂alkyl optionally substituted with one to        two substituents selected from oxo, halogen, C₁-C₃alkyl and        C₁-C₃haloalkyl, C₁-C₃haloalkyl, C₁-C₃haloalkysulfanyl,        C₁-C₃haloalkysulfonyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, or CN; or    -   C. halogen, C₁-C₃haloalkyl, C₁-C₃haloalkylsulfanyl,        C₁-C₃haloalkysulfonyl, or C₁-C₃haloalkoxy; or    -   D. halogen, C₁-C₂haloalkyl, C₁-C₂haloalkylsulfanyl,        C₁-C₂haloalkysulfonyl, or C₁-C₂haloalkoxy; or    -   E. chlorine, fluorine, bromine, iodine, difluoromethyl,        trifluoromethyl, trifluoromethylsulfanyl,        trifluoromethylsulfonyl; or    -   F. fluorine, chlorine, bromine, iodine, trifluoromethylsulfanyl,        trifluoromethylsulfonyl or trifluoromethyl; or    -   G. trifluoromethyl, fluorine, bromine or chlorine.

In an embodiment of each aspect of the invention, R₃ is

-   -   A. C₁-C₃alkyl or C₁-C₃haloalkyl; or    -   B. methyl or trifluromethyl; or    -   C. methyl.

In an embodiment of each aspect of the invention, Q is

-   -   A. Q^(a); or    -   B. Q^(b).

In an embodiment of each aspect of the invention, Q^(a) is

-   -   A. selected from Q^(a)-1 to Q^(a)-16; or    -   B. selected from Q^(a)-1, Q^(a)-6, Q^(a)-7, Q^(a)-10, and        Q^(a)-15; or    -   C. Q^(a)-1 or Q^(a)-15.

In an embodiment of each aspect of the invention, Q^(b) is

-   -   A. selected from Q^(b)-1 to Q^(b)-13; or    -   B. Q^(b)-1.

In an embodiment of each aspect of the invention, R₄ is

-   -   A. pyridine, or pyrimidine; wherein the pyridine or pyrimidine,        independently of each other, is optionally substituted with one        substituent selected from C₁-C₃alkyl, C₁-C₃haloalkyl,        C₁-C₃alkoxy, C₃-C₄cycloalkyl, halo, hydroxyl, ON,        C₁-C₆haloalkoxy, C₂-C₆haloalkenyloxy, C₂-C₆haloalkynyloxy,        C₃-C₄halocycloalkoxy, C₃-C₆cycloalkylC₁-C₄haloalkoxy, NH₂C(O)—,        NH₂C(S)—, (OH)N═C(NH₂)—, J-13 optionally substituted by 1 to 3        substituents independently selected from halogen, C₁-C₃alkyl,        C₁-C₃haloalkyl, C₁-C₃alkoxy and C₁-C₃haloalkoxy, J-20 optionally        substituted by 1 to 3 substituents independently selected from        halogen, C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy and        C₁-C₃haloalkoxy and 1H-tetrazol-5-yl; or    -   B. pyridine or pyrimidine, wherein the pyridine or pyrimidine,        independently of each other, is optionally substituted with one        substituent selected from C₁-C₃alkyl, C₁-C₃haloalkyl,        C₁-C₃alkoxy, C₃-C₄cycloalkyl, halo, hydroxyl, ON,        C₁-C₆haloalkoxy, C₂-C₆haloalkenyloxy, C₂-C₆haloalkynyloxy,        C₃-C₄halocycloalkoxy, C₃-C₆cycloalkylC₁-C₄haloalkoxy, NH₂C(O)—,        NH₂C(S)—, (OH)N═C(NH₂)—, J-13 optionally substituted by        C₁-C₃haloalkyl, J-20 optionally substituted by C₁-C₃haloalkyl        and 1H-tetrazol-5-yl; or    -   C. pyridine, wherein the pyridine is optionally substituted with        one substituent selected from C₁-C₃alkyl, C₁-C₃haloalkyl,        C₁-C₃alkoxy, C₃-C₄cycloalkyl, halo, hydroxyl, ON,        C₁-C₆haloalkoxy, C₂-C₆haloalkenyloxy, C₂-C₆haloalkynyloxy,        C₃-C₄halocycloalkoxy, C₃-C₆cycloalkylC₁-C₄haloalkoxy, NH₂C(O)—,        NH₂C(S)—, (OH)N═C(NH₂)—, J-13 optionally substituted by        C₁-C₃haloalkyl, J-20 optionally substituted by C₁-C₃haloalkyl        and 1H-tetrazol-5-yl; or    -   D. pyrimidine; wherein the pyrimidine is optionally substituted        with one substituent selected from C₁-C₃alkyl, C₁-C₃haloalkyl,        C₁-C₃alkoxy, C₃-C₄cycloalkyl, halo, hydroxyl, CN,        C₁-C₆haloalkoxy, C₂-C₆haloalkenyloxy, C₂-C₆haloalkynyloxy,        C₃-C₄halocycloalkoxy, C₃-C₆cycloalkylC₁-C₄haloalkoxy, NH₂C(O)—,        NH₂C(S)—, (OH)N═C(NH₂)—, J-13 optionally substituted by        trifluoromethyl, J-20 optionally substituted by trifluoromethyl        and 1H-tetrazol-5-yl; or    -   E. pyridine, pyrimidine, pyrazine or pyridazine, wherein the        pyridine, pyrimidine, pyrazine or pyridazine is optionally        substituted with one substituent selected from C₁-C₃alkyl,        C₁-C₃haloalkyl, C₁-C₃alkoxy, C₃-C₄cycloalkyl, F, Cl, Br, CN, and        C₁-C₆haloalkoxy; or    -   F. pyridine, pyrimidine, pyrazine or pyridazine, wherein the        pyridine, pyrimidine, pyrazine or pyridazine is optionally        substituted with one substituent selected from C₁-C₃alkyl,        C₃-C₄cycloalkyl, F, Cl, Br, CN, and C₁-C₆haloalkoxy; or    -   G. pyridine, pyrimidine, pyrazine or pyridazine, wherein the        pyridine, pyrimidine, pyrazine or pyridazine is optionally        substituted with one substituent selected from cyclopropyl, F,        Cl, Br, CN, trifluoromethoxy, difluoromethoxy,        2,2-difluoroethoxy and 2,2,2-trifluoroethoxy;    -   H. pyridine, or pyrimidine, wherein the pyridine or pyrimidine        is optionally substituted with one substituent selected from        cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy,        2,2-difluoroethoxy and 2,2,2-trifluoroethoxy; or    -   I. 5-cylopropylpyridine, 5-fluoropyridine, 5-chloropyridine,        5-bromopyridine, 5-difluoromethoxypyridine,        5-trifluoromethoxypyridine, 5-cyanopyridine,        5-(2,2-difluoroethoxy)-pyridine,        5-(2,2,2-trifluoroethoxy)-pyridine, pyridine,        5-cylopropylpyrimidine, 5-fluoropyrimidine, 5-chloropyrimidine,        5-bromopyrimidine, 5-difluoromethoxypyrimidine,        5-trifluoromethoxypyrimidine, 5-cyanopyrimidine,        5-(2,2-difluoroethoxy)-pyrimidine,        5-(2,2,2-trifluoroethoxy)-pyrimidine, or pyrimidine; or    -   J. 5-cylopropylpyridin-2-yl, 5-fluoropyridin-2-yl,        5-chloropyridin-2-yl, 5-bromopyridin-2-yl,        5-difluoromethoxypyridin-2-yl, 5-trifluoromethoxypyridin-2-yl,        5-cyanopyridin-2-yl, 5-(2,2-difluoroethoxy-pyridin-2-yl,        5-(2,2,2-trifluoroethoxy)-pyridin-2-yl, pyridin-2-yl,        5-cylopropylpyrimidin-2-yl, 5-fluoropyrimidin-2-yl,        5-chloropyrimidin-2-yl, 5-bromopyrimidin-2-yl,        5-difluoromethoxypyrimidin-2-yl,        5-trifluoromethoxypyrimidin-2-yl, 5-cyanopyrimidin-2-yl,        5-(2,2-difluoroethoxy)-pyrimidin-2-yl,        5-(2,2,2-trifluoroethoxy)-pyrimidin-2-yl, or pyrimidin-2-yl; or    -   K. pyrimidin-2-yl, pyridin-2-yl, 5-bromopyrimidin-2-yl,        5-bromopyridin-2-yl, 5-cyanopyrimidin-2-yl, or        5-cyanopyridin-2-yl; or    -   L. pyrimidin-2-yl, 5-bromopyrimidin-2-yl, 5-bromopyridin-2-yl,        or 5-cyanopyridin-2-yl.

In an embodiment of each aspect of the invention, R_(4a) is

-   -   A. pyridine, pyrimidine, pyrazine or pyridazine, wherein the        pyridine, pyrimidine, pyrazine or pyridazine, independent of        each other, is optionally substituted with one substituent        selected from C₁-C₃haloalkyl, C₃-C₄cycloalkyl, halogen, cyano,        C₁-C₃haloalkoxy and selected from Y-1 to Y-4; or    -   B. pyridine, pyrimidine, pyrazine or pyridazine, wherein the        pyridine, pyrimidine, pyrazine or pyridazine, independent of        each other, is optionally substituted with one substituent        selected from F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy,        2,2-difluoroethoxy and 2,2,2-trifluoroethoxy and selected from        Y-1 to Y-4; or    -   C. pyridine or, pyrimidine, wherein the pyridine or pyrimidine        is optionally substituted with one substituent selected from        C₁-C₃haloalkyl, C₃-C₄cycloalkyl, halogen, cyano, C₁-C₃haloalkoxy        and selected from Y-1 to Y-4; or    -   D. pyridine or, pyrimidine, wherein the pyridine or pyrimidine        is optionally substituted with one substituent selected from        cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy,        2,2-difluoroethoxy and 2,2,2-trifluoroethoxy and selected from        Y-1 to Y-4; or    -   E. 5-cylopropylpyridine, 5-fluoropyridine, 5-chloropyridine,        5-bromopyridine, 5-difluoromethoxypyridine,        5-trifluoromethoxypyridine, 5-cyanopyridine,        5-(2,2-difluoroethoxy)-pyridine,        5-(2,2,2-trifluoroethoxy)-pyridine, pyridine,        5-cylopropylpyrimidine, 5-fluoropyrimidine, 5-chloropyrimidine,        5-bromopyrimidine, 5-difluoromethoxypyrimidine,        5-trifluoromethoxypyrimidine, 5-cyanopyrimidine,        5-(2,2-difluoroethoxy)-pyrimidine,        5-(2,2,2-trifluoroethoxy)-pyrimidine, pyrimidine, or        1,2,3-triazole; or    -   F. 5-cylopropylpyridin-2-yl, 5-fluoropyridin-2-yl,        5-chloropyridin-2-yl, 5-bromopyridin-2-yl,        5-difluoromethoxypyridin-2-yl, 5-trifluoromethoxypyridin-2-yl,        5-cyanopyridin-2-yl, 5-(2,2-difluoroethoxy)-pyridin-2-yl,        5-(2,2,2-trifluoroethoxy)-pyridin-2-yl, pyridin-2-yl,        5-cylopropylpyrimidin-2-yl, 5-fluoropyrimidin-2-yl,        5-chloropyrimidin-2-yl, 5-bromopyrimidin-2-yl,        5-difluoromethoxypyrimidin-2-yl,        5-trifluoromethoxypyrimidin-2-yl, 5-cyanopyrimidin-2-yl,        5-(2,2-difluoroethoxy)-pyrimidin-2-yl,        5-(2,2,2-trifluoroethoxy)-pyrimidin-2-yl, pyrimidin-2-yl, or        1,2,3-triazol-2-yl (or Y2); or    -   G. 1,2,3-triazol-2-yl (or Y2), pyrimidin-2-yl, or        5-cyanopyridin-2-yl.

In an embodiment of each aspect of the invention, when Y-1 is selectedas R_(4a), R′_(4a) and R′_(4c), independently of each other, are

-   -   A. hydrogen, halogen, CN, C₁-C₃alkyl, C₁-C₃haloalkyl,        C₃-C₄cycloalkyl, C₁-C₃alkoxy, and C₁-C₃haloalkoxy; or    -   B. from hydrogen, F, Cl, Br, CN, methyl, CF₃, cyclopropyl,        methoxy and difluoromethoxy; or    -   C. both hydrogen.

In an embodiment of each aspect of the invention, when Y-2 is selectedas R_(4a),

-   -   A. R′_(4b) and R′_(4c), independently of each other, are        selected from hydrogen, halogen, CN, C₁-C₃alkyl, C₁-C₃haloalkyl,        C₃-C₄cycloalkyl, C₁-C₃alkoxy, and C₁-C₃haloalkoxy; or    -   B. R′_(4b) and R′_(4c), independently of each other, are        selected from hydrogen, F, Cl, Br, CN, methyl, CF₃, cyclopropyl,        methoxy and difluoromethoxy; or    -   A. R′_(4b) and R′_(4c) are both hydrogen; or    -   B. R′_(4b) is hydrogen and R′_(4c) is cyclopropyl.

In an embodiment of each aspect of the invention, when Y-3 is selectedas R_(4a), R′_(4a) and R′_(4b), independently of each other, are

-   -   A. hydrogen, halogen, CN, C₁-C₃alkyl, C₁-C₃haloalkyl,        C₃-C₄cycloalkyl, C₁-C₃alkoxy, and C₁-C₃haloalkoxy; or    -   B. hydrogen, F, Cl, Br, CN, methyl, CF₃, cyclopropyl, methoxy        and difluoromethoxy; or    -   C. both hydrogen.

In an embodiment of each aspect of the invention, when Y-4 is selectedas R′_(4a),

-   -   A. R′_(4a), R′_(4b), and R′_(4c) are, independently of each        other, selected from hydrogen, halogen, CN, C₁-C₃alkyl,        C₁-C₃haloalkyl, C₃-C₄cycloalkyl, C₁-C₃alkoxy, and        C₁-C₃haloalkoxy; or    -   B. R′_(4a), R′_(4b), and R′_(4c) are, independently of each        other, selected from hydrogen, F, Cl, Br, CN, methyl, CF₃,        cyclopropyl, methoxy and difluoromethoxy; or    -   C. R′_(4a), R′_(4b), and R′_(4c) are all hydrogen; or    -   D. R′_(4a) and R′_(4c) are hydrogen and R′_(4b) is CN.

In an embodiment of each aspect of the invention, R₅ is

-   -   A. hydrogen, C₁-C₃alkyl, C₁-C₃haloalkyl, C₃-C₄cycloalkyl,        C₁-C₃alkoxy, halogen, C₁-C₃alkoxy-C₁-C₃alkyl,        C₁-C₃alkoxy-C₁-C₃alkoxy-C₁-C₃alkyl, (C₁-C₃alkyl)C(O),        (C₁-C₃alkoxy)C(O), HC(O), C₁-C₃haloalkoxy or a 5-membered        heteroaromatic ring wherein the 5-membered heteroaromatic ring        can be optionally substituted with one to three substituents        selected from C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,        C₃-C₄cycloalkyl, halogen, CN or hydroxy; or    -   B. hydrogen, C₁-C₃alkyl, C₁-C₃haloalkyl, C₃-C₄cycloalkyl,        C₁-C₃alkoxy, halogen, C₁-C₃alkoxy-C₁-C₃alkyl,        C₁-C₃alkoxy-C₁-C₃alkoxy-C₁-C₃alkyl, (C₁-C₃alkyl)C(O),        (C₁-C₃alkoxy)C(O), HC(O) or C₁-C₃haloalkoxy; or    -   C. hydrogen, C₁-C₃alkyl, C₁-C₃haloalkyl, C₃-C₄cycloalkyl,        C₁-C₃alkoxy, halogen, C, Br, C₁-C₃alkoxy-C₁-C₃alkyl,        C₁-C₃alkoxy-C₁-C₃alkoxy-C₁-C₃alkyl, (C₁-C₃alkyl)C(O),        (C₁-C₃alkoxy)C(O), or C₁-C₂haloalkoxy; or    -   D. hydrogen, C₁-C₃alkyl, C₁-C₃alkoxy, C₃-C₄cycloalkyl,        C₁-C₃haloalkoxy, halogen, C₁-C₃alkoxy-C₁-C₃alkyl,        C₁-C₃alkoxy-C₁-C₃alkoxy-C₁-C₃alkyl, (C₁-C₃alkyl)C(O), HC(O), or        (C₁-C₃alkoxy)C(O); or    -   E. hydrogen, C₁-C₂alkyl, C₁-C₂alkoxy, C₃-C₄cycloalkyl,        C₁-C₂haloalkoxy, halogen, C₁-C₂alkoxy-C₁-C₂alkyl,        C₁-C₂alkoxy-C₁-C₂alkoxy-C₁-C₂alkyl, (C₁-C₂alkyl)C(O), HC(O), or        (C₁-C₂alkoxy)C(O); or    -   F. hydrogen, methyl, trifluoromethoxy, methoxy, cyclopropyl,        2,2-difluroroethoxy, 2,2,2-trifluroroethoxy, difluoromethoxy,        2,2,2-trifluroroethyl, chloro, bromo, methoxyethoxy,        methylcarbonyl, or methoxycarbonyl; or    -   G. hydrogen.

In an embodiment of each aspect of the invention, R_(5a) is

-   -   A. hydrogen, halogen, CN, C₁-C₃alkyl, C₁-C₃haloalkyl,        C₃-C₄cycloalkyl, C₁-C₃alkoxy or C₁-C₃haloalkoxy; or    -   B. hydrogen, halogen, CN, C₁-C₃alkyl, C₁-C₃haloalkyl,        C₃-C₄cycloalkyl or C₁-C₃alkoxy; or    -   C. hydrogen, halogen, CN, C₁-C₃alkyl, C₁-C₃haloalkyl or        C₁-C₃alkoxy; or    -   D. hydrogen, halogen, CN, C₁-C₃alkyl or C₁-C₃alkoxy; or    -   E. hydrogen or halogen; or    -   F. hydrogen.

In an embodiment of each aspect of the invention, R_(5b) is

-   -   A. hydrogen, halogen, CN, C₁-C₃haloalkyl, C₃-C₄cycloalkyl,        C₁-C₃alkoxy, or C₁-C₃haloalkoxy; or    -   B. hydrogen, halogen or C₁-C₃alkoxy; or    -   C. hydrogen.

In an embodiment of each aspect of the invention, R₆ is

-   -   A. phenyl, benzyl, heteroaryl, or C₃-C₆ cycloalkyl, each of        which, independent of each other, is optionally substituted with        one substituent selected from R_(x); or    -   B. phenyl, benzyl, cyclopropyl or cyclopropyl substituted with        one substituent selected from R_(x).

In an embodiment of each aspect of the invention, R_(x) is independentlyselected from

-   -   A. halogen, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy or CN;        or    -   B. F, C, Br, OCF₂H, OCH₃ or CN.

In an embodiment of each aspect of the invention, R_(Z) is independentlyselected from

-   -   A. oxo, halogen, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy or        CN; or    -   B. oxo, F, C, Br, OCF₂H, OCH₃ or CN.

In an embodiment of each aspect of the invention, R_(Y) is independentlyselected from

-   -   A. hydrogen, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, C₁-C₃        haloalkoxy, halogen, CN and cyclopropyl; or    -   B. hydrogen, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, C₁-C₃        haloalkoxy, halogen, and cyclopropyl; or    -   C. hydrogen, C₁-C₃ alkyl, C₁-C₃ haloalkyl, and C₁-C₃ alkoxy; or    -   D. hydrogen, methyl, trifluoromethyl, and methoxy; or    -   E. hydrogen.

The present invention, accordingly, makes available a compound offormula I having the substituents R₁, R_(2a), R_(2b), R₃, Q, A₁, A₂, A₃,A₄, and A₅ as defined above in all combinations/each permutation.Accordingly, made available, for example, is a compound of formula Iwith A₁, A₂, and A₃ being of the first aspect (i.e. A₁, A₂ and A₃ are,independently from each other, N or CR_(Y); and where R_(Y) is ofembodiment D (i.e, R_(Y) is independently selected from hydrogen,methyl, trifluoromethyl, and methoxy); A₄, and A₅ being of theembodiment B (i.e. A₄ is CR_(Y), and A₅ is CH where R_(Y) is ofembodiment B (i.e, R_(Y) hydrogen, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃alkoxy, C₁-C₃ haloalkoxy, halogen, or cyclopropyl); R₁ being embodimentB (i.e. hydrogen, C₁-C₆alkyl, C₁-C₆cyanoalkyl, aminocarbonylC₁-C₆alkyl,hydroxycarbonylC₁-C₆alkyl, C₁-C₆nitroalkyl, trimethylsilaneC₁-C₆alkyl,C₁-C₃alkoxy-C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl,C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₄cycloalkylC₁-C₂alkyl-,benzyloxycarbonyl, or benzyl); R_(2a) being an embodiment L (i.e.halogen, C₁-C₂haloalkyl, C₁-C₂haloalkylsulfanyl, C₁-C₂haloalkysulfonyl,or C₁-C₂haloalkoxy); R_(2b) being embodiment B (i.e. halogen,C₁-C₃haloalkyl, or C₁-C₃haloalkoxy); R₃ being embodiment B (i.e.hydrogen, halogen, C₃-C₄cycloalkyl, cyclopropylcarbonyl,C₃-C₄cycloalkyl-C₁-C₂alkyl optionally substituted with one to twosubstituents selected from oxo, halogen, C₁-C₃alkyl and C₁-C₃haloalkyl,C₁-C₃haloalkyl, C₁-C₃haloalkysulfanyl, C₁-C₃haloalkysulfonyl,C₁-C₃alkoxy, C₁-C₃haloalkoxy, or CN); Q being embodiment A (i.e. Q isQ^(a), wherein Q^(a) can be embodiment B (i.e. Q^(a) is selected fromQ^(a)-1, Q^(a)-6, Q^(a)-7, Q^(a)-10, and Q^(a)-15; and R⁴ is embodimentG (i.e. pyridine, or pyrimidine, wherein the pyridine or pyrimidine isoptionally substituted with one substituent selected from cyclopropyl,F, C, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and2,2,2-trifluoroethoxy).

In an embodiment, the compound of formula I is formula Iaa, Iab or Iac(with asterisk indicating a stereogenic centre), wherein R₁, R_(2a),R_(2b), and R₃, are as defined in the first aspect and Q₁ corresponds toQ as defined in the first aspect, each with the correspondingembodiments as described above.

In an embodiment, compounds having preferred stereochemistry depicted informula I′a would also be preferred for compounds of formulae Iaa, Iaband Iac. In an preferred embodiment, a compound of formula Iab with thefollowing stereochemistry is preferred:

where R₁, R_(2a), R_(2b), R₃, Q₁ are as defined in the first aspect, andstereoisomers, enantiomers, tautomers and N-oxides of the compounds offormula (I′ab), and agrochemically acceptable salts thereof.

In an embodiment, Q₁ is

-   -   A. selected from Q^(aa) to Q^(ag) and Q^(ba) to Q^(bf); or    -   B. selected from Q^(aa) to Q^(ag); or    -   C. selected from Q^(ba) to Q^(bf); or    -   D. selected from Q^(aa), Q^(ab), Q^(ac), Q^(af), Q^(ag), Q^(ba),        Q^(bb), Q^(bc), Q^(bd), Q^(be) and Q^(bf); or    -   E. selected from Q^(aa), Q^(ab), Q^(ac), Q^(af), Q^(af), Q^(ba),        Q^(bb) and Q^(bf); or    -   F. selected from Q^(aa), Q^(ab), Q^(ac), Q^(af), Q^(b)a, Q^(bb)        and Q^(bf).

In an embodiment of each aspect of the invention, the compound offormula I has as A₁, A₂ and A₃, independently from each other, N orCR_(Y) (wherein R_(Y) is hydrogen, methyl, trifluoromethyl, andmethoxy); as A₄ N or OH and A₅ as OH; as R₁ hydrogen, methyl, propargylor cyclopropyl-methyl; as R_(2a) hydrogen, halogen, C₁-C₃alkyl,C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, cyclopropyl, cyclopropylsubstituted with one to two substituents independently selected fromhalogen, methyl, and trifluoromethyl, cyclopropylcarbonyl,cyclopropylmethyl substituted with one to two substituents independentlyselected from oxo, halogen, and trifluomethyl, or C₁-C₂alkylsulfanylsubstituted with one to three halogens or C₁-C₂alkylsulfonyl substitutedwith one to three halogens; as R_(2b) hydrogen, halogen,C₃-C₄cycloalkyl, cyclopropylcarbonyl, C₃-C₄cycloalkyl-C₁-C₂alkyloptionally substituted with one to two substituents selected from oxo,halogen, C₁-C₃alkyl and C₁-C₃haloalkyl, C₁-C₃haloalkyl,C₁-C₃haloalkysulfanyl, C₁-C₃haloalkysulfonyl, C₁-C₃alkoxy,C₁-C₃haloalkoxy, or ON; as R₃ methyl; and as Q selected from Q^(a)-1 toQ^(a)-16 and Q^(b)-1 to Q^(b)-13, where as R₄ (for Q^(a)-1 to Q^(a)-16)is pyridine or pyrimidine, wherein the pyridine or pyrimidine,independently of each other, is optionally substituted with onesubstituent selected from C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,C₃-C₄cycloalkyl, halo, hydroxyl, ON, C₁-C₆haloalkoxy,C₂-C₆haloalkenyloxy, C₂-C₆haloalkynyloxy, C₃-C₄halocycloalkoxy,C₃-C₆cycloalkylC₁-C₄haloalkoxy, NH₂C(O)—, NH₂C(S)—, (OH)N═C(NH₂)—, J-13optionally substituted by C₁-C₃haloalkyl, J-20 optionally substituted byC₁-C₃haloalkyl and 1H-tetrazol-5-yl; and R_(4a) (for Q^(b)-1 toQ^(b)-13) is pyridine or, pyrimidine, wherein the pyridine or pyrimidineis optionally substituted with one substituent selected fromC₁-C₃haloalkyl, C₃-C₄cycloalkyl, halogen, cyano, C₁-C₃haloalkoxy andselected from Y-1 to Y-4 (where R′_(4a), R′_(4b), and R′_(4c),independently of each other and independently of Y-1 to Y-4, areselected from hydrogen, halogen, ON, C₁-C₃alkyl, C₁-C₃haloalkyl,C₃-C₄cycloalkyl, C₁-C₃alkoxy, and C₁-C₃haloalkoxy).

In an embodiment of each aspect of the invention, the compound offormula I is represented by formula Iaa, Iab or Iac, has as R₁ hydrogen,methyl, propargyl or cyclopropyl-methyl; as R_(2a) hydrogen, halogen,C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, cyclopropyl,cyclopropyl substituted with one to two substituents independentlyselected from halogen, methyl, and trifluoromethyl, cyclopropylcarbonyl,cyclopropylmethyl substituted with one to two substituents independentlyselected from oxo, halogen, and trifluomethyl, or C₁-C₂alkylsulfanylsubstituted with one to three halogens or C₁-C₂alkylsulfonyl substitutedwith one to three halogens; as R_(2b) hydrogen, halogen,C₃-C₄cycloalkyl, cyclopropylcarbonyl, C₃-C₄cycloalkyl-C₁-C₂alkyloptionally substituted with one to two substituents selected from oxo,halogen, C₁-C₃alkyl and C₁-C₃haloalkyl, C₁-C₃haloalkyl,C₁-C₃haloalkysulfanyl, C₁-C₃haloalkysulfonyl, C₁-C₃alkoxy,C₁-C₃haloalkoxy, or CN; as R₃ methyl; and as Q selected from Q^(a)-1 toQ^(a)-16 and Q^(b)-1 to Q^(b)-13, where as R₄ (for Q^(a)-1 to Q^(a)-16)is pyridine or pyrimidine, wherein the pyridine or pyrimidine,independently of each other, is optionally substituted with onesubstituent selected from C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,C₃-C₄cycloalkyl, halo, hydroxyl, CN, C₁-C₆haloalkoxy,C₂-C₆haloalkenyloxy, C₂-C₆haloalkynyloxy, C₃-C₄halocycloalkoxy,C₃-C₆cycloalkylC₁-C₄haloalkoxy, NH₂C(O)—, NH₂C(S)—, (OH)N═C(NH₂)—, J-13optionally substituted by C₁-C₃haloalkyl, J-20 optionally substituted byC₁-C₃haloalkyl and 1H-tetrazol-5-yl; and R_(4a) (for Q^(b)-1 toQ^(b)-13) is pyridine or, pyrimidine, wherein the pyridine or pyrimidineis optionally substituted with one substituent selected fromC₁-C₃haloalkyl, C₃-C₄cycloalkyl, halogen, cyano, C₁-C₃haloalkoxy andselected from Y-1 to Y-4 (where R′_(4a), R′_(4b), and R′_(4c),independently of each other and independently of Y-1 to Y-4, areselected from hydrogen, halogen, CN, C₁-C₃alkyl, C₁-C₃haloalkyl,C₃-C₄cycloalkyl, C₁-C₃alkoxy, and C₁-C₃haloalkoxy).

In an embodiment of each aspect of the invention, the compound offormula I is represented by formula Iaa, Iab or Iac, has as R₁ hydrogen,methyl, propargyl or cyclopropyl-methyl; as R_(2a) halogen,C₁-C₃haloalkyl, C₁-C₃haloalkylsulfanyl, C₁-C₃haloalkysulfonyl, orC₁-C₃haloalkoxy; as R_(2b) halogen, C₁-C₃haloalkyl,C₁-C₃haloalkylsulfanyl, C₁-C₃haloalkysulfonyl, or C₁-C₃haloalkoxy; as R₃methyl; and as Q selected from Q^(a)-1 to Q^(a)-16 and Q^(b)-1 toQ^(b)-13, where as R₄ (for Q^(a)-1 to Q^(a)-16) is pyridine orpyrimidine, wherein the pyridine or pyrimidine, independently of eachother, is optionally substituted with one substituent selected fromC₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₃-C₄cycloalkyl, halo,hydroxyl, CN, C₁-C₆haloalkoxy, C₂-C₆haloalkenyloxy, C₂-C₆haloalkynyloxy,C₃-C₄halocycloalkoxy, C₃-C₆cycloalkylC₁-C₄haloalkoxy, NH₂C(O)—,NH₂C(S)—, (OH)N═C(NH₂)—, J-13 optionally substituted by C₁-C₃haloalkyl,J-20 optionally substituted by C₁-C₃haloalkyl and 1H-tetrazol-5-yl; andR_(4a) (for Q^(b)-1 to Q^(b)-13) is pyridine or, pyrimidine, wherein thepyridine or pyrimidine is optionally substituted with one substituentselected from C₁-C₃haloalkyl, C₃-C₄cycloalkyl, halogen, cyano,C₁-C₃haloalkoxy and selected from Y-1 to Y-4 (where R′_(4a), R′_(4b),and R′_(4c), independently of each other and independently of Y-1 toY-4, are selected from hydrogen, halogen, CN, C₁-C₃alkyl,C₁-C₃haloalkyl, C₃-C₄cycloalkyl, C₁-C₃alkoxy, and C₁-C₃haloalkoxy).

In an embodiment of each aspect of the invention, the compound offormula I is represented by formula Iaa, Iab or Iac, has as R₁ hydrogen,methyl, propargyl or cyclopropyl-methyl; as R_(2a) halogen,C₁-C₃haloalkyl, C₁-C₃haloalkylsulfanyl, C₁-C₃haloalkysulfonyl, orC₁-C₃haloalkoxy; as R_(2b) halogen, C₁-C₃haloalkyl,C₁-C₃haloalkylsulfanyl, C₁-C₃haloalkysulfonyl, or C₁-C₃haloalkoxy; as R₃methyl; and as Q selected from Q^(a)-1 to Q^(a)-16 and Q^(b)-1 toQ^(b)-13, where as R₄ (for Q^(a)-1 to Q^(a)-16) is pyridine orpyrimidine, wherein the pyridine or pyrimidine, independently of eachother, is optionally substituted with one substituent selected fromC₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₃-C₄cycloalkyl, halo,hydroxyl, CN, C₁-C₆haloalkoxy, C₂-C₆haloalkenyloxy, C₂-C₆haloalkynyloxy,C₃-C₄halocycloalkoxy, C₃-C₆cycloalkylC₁-C₄haloalkoxy, NH₂C(O)—,NH₂C(S)—, (OH)N═C(NH₂)—, J-13 optionally substituted by C₁-C₃haloalkyl,J-20 optionally substituted by C₁-C₃haloalkyl and 1H-tetrazol-5-yl; andR_(4a) (for Q^(b)-1 to Q^(b)-13) is pyridine or, pyrimidine, wherein thepyridine or pyrimidine is optionally substituted with one substituentselected from C₁-C₃haloalkyl, C₃-C₄cycloalkyl, halogen, cyano,C₁-C₃haloalkoxy and selected from Y-1 to Y-4 (where R′_(4a), R′_(4b),and R′_(4c) are each hydrogen).

In an embodiment of each aspect of the invention, the compound offormula I is represented by formula Iaa, Iab or Iac, has as R₁ hydrogen,methyl, propargyl or cyclopropyl-methyl; as R_(2a) halogen,C₁-C₂haloalkyl, C₁-C₂haloalkylsulfanyl, C₁-C₂haloalkysulfonyl, orC₁-C₂haloalkoxy; as R_(2b) halogen, C₁-C₂haloalkyl,C₁-C₂haloalkylsulfanyl, C₁-C₂haloalkysulfonyl, or C₁-C₂haloalkoxy; as R₃methyl; and as Q selected from Q^(a)-1 to Q^(a)-16 and Q^(b)-1 toQ^(b)-13, where as R₄ (for Q^(a)-1 to Q^(a)-16) is pyridine orpyrimidine, wherein the pyridine or pyrimidine, independently of eachother, is optionally substituted with one substituent selected fromC₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₃-C₄cycloalkyl, halo,hydroxyl, CN, C₁-C₆haloalkoxy, C₂-C₆haloalkenyloxy, C₂-C₆haloalkynyloxy,C₃-C₄halocycloalkoxy, C₃-C₆cycloalkylC₁-C₄haloalkoxy, NH₂C(O)—,NH₂C(S)—, (OH)N═C(NH₂)—, J-13 optionally substituted by C₁-C₃haloalkyl,J-20 optionally substituted by C₁-C₃haloalkyl and 1H-tetrazol-5-yl; andR_(4a) (for Q^(b)-1 to Q^(b)-13) is pyridine or, pyrimidine, wherein thepyridine or pyrimidine is optionally substituted with one substituentselected from C₁-C₃haloalkyl, C₃-C₄cycloalkyl, halogen, cyano,C₁-C₃haloalkoxy and selected from Y-1 to Y-4 (where R′_(4a), R′_(4b),and R′_(4c) are each hydrogen).

In an embodiment of each aspect of the invention, the compound offormula I is represented by formula Iaa, Iab or Iac, has as R₁ hydrogen,methyl, propargyl or cyclopropyl-methyl; as R_(2a) halogen,C₁-C₂haloalkyl, C₁-C₂haloalkylsulfanyl, C₁-C₂haloalkysulfonyl, orC₁-C₂haloalkoxy; as R_(2b) halogen, C₁-C₂haloalkyl,C₁-C₂haloalkylsulfanyl, C₁-C₂haloalkysulfonyl, or C₁-C₂haloalkoxy; as R₃methyl; and as Q selected from Q^(a)-1 or Q^(b)-1, where as R₄ (forQ^(a)-1) is pyridine or pyrimidine, wherein the pyridine or pyrimidine,independently of each other, is optionally substituted with onesubstituent selected from C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,C₃-C₄cycloalkyl, halo, hydroxyl, CN, C₁-C₆haloalkoxy,C₂-C₆haloalkenyloxy, C₂-C₆haloalkynyloxy, C₃-C₄halocycloalkoxy,C₃-C₆cycloalkylC₁-C₄haloalkoxy, NH₂C(O)—, NH₂C(S)—, (OH)N═C(NH₂)—, J-13optionally substituted by C₁-C₃haloalkyl, J-20 optionally substituted byC₁-C₃haloalkyl and 1H-tetrazol-5-yl; and R_(4a) (for Q^(b)-1) ispyridine or, pyrimidine, wherein the pyridine or pyrimidine isoptionally substituted with one substituent selected fromC₁-C₃haloalkyl, C₃-C₄cycloalkyl, halogen, cyano, C₁-C₃haloalkoxy andselected from Y-1 to Y-4 (where R′_(4a), R′_(4b), and R′_(4c) are eachhydrogen).

In an embodiment of each aspect of the invention, the compound offormula I is represented by formula Iaa, Iab or Iac, has as R₁ hydrogen,methyl, propargyl or cyclopropyl-methyl; as R_(2a) chlorine, fluorine,bromine, iodine, difluoromethyl, trifluoromethyl,trifluoromethylsulfanyl, or trifluoromethylsulfonyl; as R_(2b) chlorine,fluorine, bromine, iodine, difluoromethyl, trifluoromethyl,trifluoromethylsulfanyl, trifluoromethylsulfonyl; as R₃ methyl; and as Qselected from Q^(a)-1 or Q^(b)-1, where as R₄ (for Q^(a)-1) is pyridineor pyrimidine, wherein the pyridine or pyrimidine, independently of eachother, is optionally substituted with one substituent selected fromC₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₃-C₄cycloalkyl, halo,hydroxyl, CN, C₁-C₆haloalkoxy, C₂-C₆haloalkenyloxy, C₂-C₆haloalkynyloxy,C₃-C₄halocycloalkoxy, C₃-C₆cycloalkylC₁-C₄haloalkoxy, NH₂C(O)—,NH₂C(S)—, (OH)N═C(NH₂)—, J-13 optionally substituted by C₁-C₃haloalkyl,J-20 optionally substituted by C₁-C₃haloalkyl and 1H-tetrazol-5-yl; andR_(4a) (for Q^(b)-1) is pyridine or, pyrimidine, wherein the pyridine orpyrimidine is optionally substituted with one substituent selected fromC₁-C₃haloalkyl, C₃-C₄cycloalkyl, halogen, cyano, C₁-C₃haloalkoxy andselected from Y-1 to Y-4 (where R′_(4a), R′_(4b), and R′_(4c) are eachhydrogen).

In an embodiment of each aspect of the invention, the compound offormula I is represented by formula Iaa, Iab or Iac, has as R₁ hydrogen,methyl, propargyl or cyclopropyl-methyl; as R_(2a) chlorine, fluorine,bromine, iodine, difluoromethyl, trifluoromethyl,trifluoromethylsulfanyl, or trifluoromethylsulfonyl; as R_(2b) chlorine,fluorine, bromine, iodine, difluoromethyl, trifluoromethyl,trifluoromethylsulfanyl, trifluoromethylsulfonyl; as R₃ methyl; and as Qselected from Q^(a)-1 or Q^(b)-1, where as R₄ (for Q^(a)-1) is pyridineor pyrimidine, wherein the pyridine or pyrimidine is optionallysubstituted with one substituent selected from cyclopropyl, F, Cl, Br,CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and2,2,2-trifluoroethoxy; and R_(4a) (for Q^(b)-1) is pyridine or,pyrimidine, wherein the pyridine or pyrimidine is optionally substitutedwith one substituent selected from cyclopropyl, F, Cl, Br, CN,trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and2,2,2-trifluoroethoxy and selected from Y-1 to Y-4 (where R′_(4a),R′_(4b), and R′_(4c) are each hydrogen).

In an embodiment of each aspect of the invention, the compound offormula I is represented by formula Iaa, Iab or Iac, has R₁ as hydrogen,methyl, propargyl or cyclopropyl-methyl; as R_(2a) chlorine, fluorine,bromine, iodine, difluoromethyl, trifluoromethyl,trifluoromethylsulfanyl, or trifluoromethylsulfonyl; as R_(2b) chlorine,fluorine, bromine, iodine, difluoromethyl, trifluoromethyl,trifluoromethylsulfanyl, trifluoromethylsulfonyl; as R₃ methyl; and as Qselected from Q^(a)-1 or Q^(b)-1, where as R₄ (for Q^(a)-1) is5-cylopropylpyridine, 5-fluoropyridine, 5-chloropyridine,5-bromopyridine, 5-difluoromethoxypyridine, 5-trifluoromethoxypyridine,5-cyanopyridine, 5-(2,2-difluoroethoxy)-pyridine,5-(2,2,2-trifluoroethoxy)-pyridine, pyridine, 5-cylopropylpyrimidine,5-fluoropyrimidine, 5-chloropyrimidine, 5-bromopyrimidine,5-difluoromethoxypyrimidine, 5-trifluoromethoxypyrimidine,5-cyanopyrimidine, 5-(2,2-difluoroethoxy)-pyrimidine,5-(2,2,2-trifluoroethoxy)-pyrimidine, or pyrimidine; and R_(4a) (forQ^(b)-1) is 5-cylopropylpyridine, 5-fluoropyridine, 5-chloropyridine,5-bromopyridine, 5-difluoromethoxypyridine, 5-trifluoromethoxypyridine,5-cyanopyridine, 5-(2,2-difluoroethoxy)-pyridine,5-(2,2,2-trifluoroethoxy)-pyridine, pyridine, 5-cylopropylpyrimidine,5-fluoropyrimidine, 5-chloropyrimidine, 5-bromopyrimidine,5-difluoromethoxypyrimidine, 5-trifluoromethoxypyrimidine,5-cyanopyrimidine, 5-(2,2-difluoroethoxy)-pyrimidine,5-(2,2,2-trifluoroethoxy)-pyrimidine, pyrimidine, or 1,2,3-triazole.

In an embodiment of each aspect of the invention, the compound offormula I is represented by formula Iab or I′ab, which has as R₁embodiment H (preferably hydrogen, methyl, propargyl orcyclopropyl-methyl); as R_(2a) embodiment N (preferably trifluoromethyl,fluorine, chlorine, or bromine); as R_(2b) embodiment F (preferablyfluorine, chlorine or trifluoromethyl); as R₃ methyl; and as Q₁ selectedfrom Q^(aa) to Q^(a9) and Q^(ba) to Q^(bf) (preferably selected fromQ^(aa), Q^(ab), Q^(ac), Q^(af), Q^(ba), Q^(bb) and Q^(bf)) In a secondaspect, the present invention makes available a composition comprising acompound of formula I as defined in the first aspect, one or moreauxiliaries and diluent, and optionally one or more other activeingredient.

In a third aspect, the present invention makes available a method ofcombating and controlling insects, acarines, nematodes or molluscs whichcomprises applying to a pest, to a locus of a pest, or to a plantsusceptible to attack by a pest an insecticidally, acaricidally,nematicidally or molluscicidally effective amount of a compound asdefined in the first aspect or a composition as defined in the secondaspect.

In a fourth aspect, the present invention makes available a method forthe protection of plant propagation material from the attack by insects,acarines, nematodes or molluscs, which comprises treating thepropagation material or the site, where the propagation material isplanted, with an effective amount of a compound of formula I as definedin the first aspect or a composition as defined in the second aspect.

In a fifth aspect, the present invention makes available a plantpropagation material, such as a seed, comprising, or treated with oradhered thereto, a compound of formula I as defined in the first aspector a composition as defined in the second aspect.

The present invention in a further aspect provides a method ofcontrolling parasites in or on an animal in need thereof comprisingadministering an effective amount of a compound of the first aspect. Thepresent invention further provides a method of controlling ectoparasiteson an animal in need thereof comprising administering an effectiveamount of a compound of formula I as defined in the first aspect. Thepresent invention further provides a method for preventing and/ortreating diseases transmitted by ectoparasites comprising administeringan effective amount of a compound of formula I as defined in the firstaspect, to an animal in need thereof.

Compounds of formula I can be prepared by those skilled in the artfollowing known methods. More specifically compounds of formulae I, andI′a, and intermediates therefor can be prepared as described below inthe schemes and examples. Certain stereogenic centers have been leftunspecified for the clarity and are not intended to limit the teachingof the schemes in any way.

The process according to the invention for preparing compounds offormula I is carried out by methods known to those skilled in the art.

Compounds of formula I can be made, for example, as shown in scheme 1.

Reaction of a compound of the formula II, wherein X1 is a leaving group,such as a halogen or sulfonate, for instance chloride, with a compoundof formula III gives a compound of the formula I, wherein A1, A2, A3,A4, A5, R1, R2a, R2b, R3 and Q have the same meaning as given above forcompounds of the formula I. The reaction can be conducted neat or in asolvent, preferably in a solvent, such as an organic solvent, forinstance acetonitrile, in a temperature range of −100 to +300° C.,preferably between ambient temperature and 200° C., with or without thepresence of a catalyst, for instance a metal catalyst, such as apalladium complex, and with or without the addition of a base, such asan inorganic base, for instance potassium carbonate, or an organic base,such as, for example, triethylamine. Compounds of the formula II areeither known, or they can be prepared by methods known to a personskilled in the art.

Compounds of formula III can be made, for example, as shown in scheme 2.Treatment of a compound of the formula V, wherein X2 is a leaving group,such as a halogen or sulfonate, for instance bromide, with an amine ofthe formula XIX gives compounds of the formula III. The reaction can beconducted neat or in a solvent, preferably in a solvent, such as anorganic solvent, for instance acetonitrile, in a temperature range of−100 to +300° C., preferably between ambient temperature and 200° C.,with or without the addition of a base, such as an inorganic base, forinstance potassium carbonate, or an organic base, such as, for example,triethylamine. Alternatively, treatment of a compound of the formula VIIwith an amine of the formula XIX gives compounds of the formula III.This reaction is done in the presence of a reducing agent, such as forexample hydrogen, or a hydride, such as sodium borohydride, with orwithout a catalyst, such as a hydrogenation catalyst, for examplepalladium on carbon, with or without the presence of an acid, such asacetic acid, or a Lewis acid, such as zinc bromide, in a solvent orwithout a solvent, such as, for instance, methanol. The reaction can beconducted in a temperature range of −100 to +300° C., preferably betweenambient temperature and 200° C. Such methods, and the range ofconditions to perform them, for the alkylation of amines and for thereductive alkylation of amines are well known to a person skilled in theart. The amines of formula XIX are either known, or they can be preparedby methods known to a person skilled in the art.

Alternatively, compounds of formula I can be made, for example, as shownin scheme 3. Reaction of an amine of the formula IV with a compound ofthe formula V, wherein X2 is a leaving group, such as a halogen orsulfonate, for instance bromide, gives a compound of formula I, whereinA1, A2, A3, A4, A5, R1, R2a, R2b, R3 and Q have the same meaning asgiven above for compounds of the formula I. The reaction can beconducted neat or in a solvent, preferably in a solvent, such as anorganic solvent, for instance acetonitrile, in a temperature range of−100 to +300° C., preferably between ambient temperature and 200° C.,with or without the addition of a base, such as an inorganic base, forinstance potassium carbonate, or an organic base, such as, for example,triethylamine. Such methods for the alkylation of amines, and the rangeof conditions to perform them, are well known to a person skilled in theart. Alternatively, reaction of an amine of the formula IVa with acompound of the formula VII gives a compound of the formula I wherein R1is H and A1, A2, A3, A4, A5, R2a, R2b, R3 and Q have the same meaning asgiven above for compounds of the formula I. This reaction is done in thepresence of a reducing agent, such as for example hydrogen, or ahydride, such as sodium borohydride, with or without a catalyst, such asa hydrogenation catalyst, for example palladium on carbon, with orwithout the presence of an acid, such as acetic acid, or a Lewis acid,such as zinc bromide, in a solvent or without a solvent, such as, forinstance, methanol. The reaction can be conducted in a temperature rangeof −100 to +300° C., preferably between ambient temperature and 200° C.Such methods for the reductive alkylation of amines, and the range ofconditions to perform them, are well known to a person skilled in theart.

Compounds of formula V can be made, for example, as shown in scheme 4.Treatment of a compound of the formula VIII with a halogenating agent,such as chlorine or bromine or N-bromosuccinimide, for example, givescompound of the formula V, wherein the leaving group Q is a halogen, forinstance chloride or bromide. This reaction is done with or without asolvent, preferably in a solvent, with or without an additive, such as aradical starter, such as, for example, benzoyl peroxide orazoisobutyronirile. The reaction can be done with or without exposure tovisible light, or to UV light, and it can be conducted in a temperaturerange of −100 to +300° C., preferably between ambient temperature and200° C. Alternatively, a compound of the formula VII can be treated witha reducing agent, followed by reaction with a sulfonyl chloride, forinstance methanesulfonyl chloride, to give a compound of the formula V,wherein the leaving group Q is a sulfonate, for instance a mesylate.This reaction can be done in a solvent, or without a solvent, in thepresence of a base, such as an inorganic base, for instance potassiumcarbonate, or an organic base, such as an amine base, for instangetrimethylamine, or without a base, and it can be conducted in atemperature range of −100 to +300° C., preferably between ambienttemperature and 200° C. A suitable reducing agent could be, for example,hydrogen, or a hydride, such as sodium borohydride, with or without acatalyst, such as a hydrogenation catalyst, for example palladium oncarbon, with or without the presence of an acid, such as acetic acid, ora Lewis acid, such as zinc bromide, in a solvent or without a solvent,such as, for instance, methanol. The reaction can be conducted in atemperature range of −100 to +300° C., preferably between ambienttemperature and 200° C. Such methods for the halogenation, the reductionof carbonyl compounds and the sulfonylation of alcohols, and the rangeof conditions to perform them, are well known to a person skilled in theart. The amines of formula VII and the compounds of formula VIII areeither known, or they can be prepared by methods known to a personskilled in the art.

Alternatively, compounds of formula I wherein R1 is different from H canbe made, for example, as shown in scheme 5. A compound of the formula Iacan be reacted with a compound of the formula VI wherein X3 is a leavinggroup, such as a halogen or sulfonate, for instance a chloride, bromide,iodide or mesylate, to give a compound of formula I, wherein A1, A2, A3,A4, A5, R1, R2a, R2b, R3 and Q have the same meaning as given above forcompounds of the formula I. This reaction can be conducted neat or in asolvent, preferably in a solvent, such as an organic solvent, forinstance acetonitrile, in a temperature range of −100 to +300° C.,preferably between ambient temperature and 200° C., with or without theaddition of a base, such as an inorganic base, for instance potassiumcarbonate, or an organic base, such as, for example, triethylamine. Suchmethods for the alkylation of amines, and the range of conditions toperform them, are well known to a person skilled in the art.

Compounds of formula Ib can be made, for example, as shown in scheme 6.Reaction of a compound of the formula II, wherein X1 is a leaving group,such as a halogen or sulfonate, for instance chloride, with a compoundof formula IX gives a compound of the formula X. The reaction can beconducted neat or in a solvent, preferably in a solvent, such as anorganic solvent, for instance acetonitrile or N,N-dimethylformamide, ina temperature range of −100 to +300° C., preferably between ambienttemperature and 200° C., with or without the presence of a catalyst, forinstance a metal catalyst, such as a palladium complex, and with orwithout the addition of a base, such as an inorganic base, for instancepotassium carbonate, or an organic base, such as, for example,triethylamine. Subsequent treatment of compound X with the knowncompound XIII gives a compound of the formula XI. This reaction can beconducted neat or in a solvent, preferably in a solvent, such as anorganic solvent, for instance dichloromethane, in a temperature range of−100 to +300° C., preferably between ambient temperature and 100° C., orbetween ambient temperature and 50° C., without a base or in thepresence of a base, such as an inorganic base, for instance potassiumcarbonate, or an organic base, such as, for example, triethylamine.Further reaction of compound XI with hydrazine XII gives the compound offormula Ib, wherein A1, A2, A3, A4, A5, R2a, R2b, R3 and R4 have thesame meaning as given above for compounds of the formula I. Thisreaction can be conducted neat or in a solvent, preferably in a solvent,such as an organic solvent, for instance 1,4-dioxane, or acetic acid, ora mixture of 1,4-dioxane and acetic acid, in a temperature range of −100to +300° C., preferably between ambient temperature and 200° C., orbetween ambient temperature and 80° C. Within this sequence oftransformations, the intermediate compounds of formula X and of formulaXI can be used as crude products for the subsequent step, or they can bepurified, for instance by chromatography, and used in purified form forthe next transformation.

Compounds of formula Ic can be made, for example, as shown in scheme 7.Reaction of a compound of the formula XVII with an amine of the formulaXIX gives compounds of the formula XVI. This reaction is done in thepresence of a reducing agent, such as for example hydrogen, or ahydride, such as sodium borohydride, with or without a catalyst, such asa hydrogenation catalyst, for example palladium on carbon, with orwithout the presence of an acid, such as acetic acid, or a Lewis acid,such as zinc bromide, in a solvent or without a solvent, such as, forinstance, methanol. The reaction can be conducted in a temperature rangeof −100 to +300° C., preferably between ambient temperature and 200° C.Such methods, and the range of conditions to perform them, for thereductive alkylation of amines are well known to a person skilled in theart. Subsequent reaction of the intermediate of the formula XVI with acompound of the formula II gives a compound of the formula XIV. Thisreaction can be conducted neat or in a solvent, preferably in a solvent,such as an organic solvent, for instance acetonitrile, in a temperaturerange of −100 to +300° C., preferably between ambient temperature and200° C., with or without the presence of a catalyst, for instance ametal catalyst, such as a palladium complex, and with or without theaddition of a base, such as an inorganic base, for instance potassiumcarbonate, or an organic base, such as, for example, triethylamine.Subsequently, the intermediate of the formula XIV is reacted with acompound of the formula XV to give the compound of formula Ic, whereinA1, A2, A3, A4, A5, R2a, R2b, R1, R3 and R4 have the same meaning asgiven above for compounds of the formula I, and M1 in R4-M1 is a metal,such as for instance lithium, or —MgCl, or —ZnBr, or —B(OH)₂; or R4-M1represents a boronate, such as a pinacol ester of a boronic acid, or astannane such as R4-Sn(n-Bu)₃. Such transformations are known to aperson skilled in the art as Suzuki-, Kumada-, Negishi- orStille-coupling reactions, respectively. Such reactions are carried outin a temperature range of −100 to +300° C., preferably between ambienttemperature and 200° C., in the presence of a catalyst, such as a metalcatalyst, for instance a palladium catalyst, and a ligand, such as forexample a phosphine ligand, or an N-heterocyclic carbene (NHC) ligand,or a phosphite ligand. The reaction can be done in the presence orabsence of an additional metal catalyst, such as, for example, a coppersalt, for instance CuI. The reaction is done with or without a base,which can be an inorganic base, such as potassium carbonate, or sodiumhydroxide, or cesium carbonate, or an organic base, such as an aminebase, for instance triethyl amine. This reaction is done with or withouta solvent, preferentially in a solvent. Where the reaction mixture isheated, the reaction can be conducted under microwave irradiation orwith conventional heating, such as heating the reaction vessel in an oilbath. By an alternative route, compound XVII can be reacted with acompound of the formula XV to give intermediate XVIII. This reaction isdone essentially under in the same range of conditions as described forthe transformation of intermediate XIV to the compound of formula Ic.Subsequently, the intermediate XVIII is reacted with amine IV to give acompound of the formula Ic, wherein R1 is hydrogen and A1, A2, A3, A4,A5, R2a, R2b, R3 and R4 have the same meaning as given above forcompounds of the formula I. This reaction is done in the presence of areducing agent, essentially under the same conditions as described abovefor the transformation of compound XVII to intermediate XVI. By yetanother alternative route, the intermediate compound of the formulaXVIII can be reacted with an amine of the formula XIX to give theintermediate of the formula IIIa. This reaction is done in the presenceof a reducing agent, essentially under the same conditions as describedabove for the transformation of compound XVII to intermediate XVI.Subsequently, the intermediate of the formula IIIa is reacted with acompound of the formula II to give the compound of the formula Ic,wherein A1, A2, A3, A4, A5, R2a, R2b, R1, R3 and R4 have the samemeaning as given above for compounds of the formula I. This reaction isdone essentially under the same conditions as described above for thetransformation of intermediate XVI to intermediate XIV. Within thesedifferent multistep sequences, the intermediate compounds of formulasXIV, XVI, XVIII and IIIa can be used as crude products for therespective subsequent step, or they can be purified, for instance bychromatography, and used in purified form for the next transformation.Compounds of the formula XVII are known, or they can be prepared bymethods known to a person skilled in the art.

Compounds of the Formula Id

can be prepared by the reaction of an amine of the formula IIIb

wherein R1, R3, R4a, R5a and R5b are as described in formula I with acompound of the formula II

wherein A1, A2, A3, A4, A5, R2a and R2b are as described in formula Iand X1 is a leaving group, such as a halogen or a sulfonate, forinstance chloride.

The chemistry is described in more detail in Scheme 8.

Reaction of a compound of the formula II, wherein X1 is a leaving group,such as a halogen or sulfonate, for instance chloride, with a compoundof formula IIIb gives a compound of the formula Id, wherein A1, A2, A3,A4, A5, R1, R2a, R2b, R3, R4a, R5a and R5b have the same meaning asgiven above for compounds of the formula I. The reaction can beconducted neat or in a solvent, preferably in a solvent, such as anorganic solvent, for instance acetonitrile, in a temperature range of−100 to +300° C., preferably between ambient temperature and 200° C.,with or without the presence of a catalyst, for instance a metalcatalyst, such as a palladium complex, and with or without the additionof a base, such as an inorganic base, for instance potassium carbonate,or an organic base, such as, for example, triethylamine.

The formation of compounds of formula IIIb is outlined in Scheme 9.Compounds of formula IIIb can be prepared by treatment of compounds offormula IIIc, wherein R₃, R_(4a), R_(5a), and R_(5b) are as described informula I, with compounds of formula XX wherein R₁ is as defined informula I, e.g. in the presence of NaBH(OAc)₃ or NaBH₃CN, in a suitablesolvent, preferably in acetic acid at room temperature analog toWO2002/088073, page 35. Alternatively, another reagent system for thereductive amination uses a combination of Ti(i-OiPr)₄ and NaBH₄ (seeSynthesis 2003 (14), 2206).

Amines of formula IIIc may be obtained by biocatalyzed deracemization ofamines of formula IIId. This may be done for instance using a lipase,e.g. Candida Antarctica lipase B or Pseudomonas fluorescens lipase,eventually in immobilized form (e.g. Novozym® 435) in presence of anacyl donor, e.g. ethyl methoxyacetate or vinyl acetate, in a suitablesolvent such as acetonitrile or methyl tert-butyl ether at temperaturesbetween 20° C. to 100° C. Such processes are described for instance inJ. Org. Chem. 2007, 72, 6918-6923 or Adv. Synth. Catal. 2007, 349,1481-1488. The expected stereochemical outcome of such enzymaticderacemization are known of those skilled in the art and are documentedin the literature, for instance in J. Org. Chem. 1991, 56, 2656-2665 orJ. Am. Chem. Soc. 2015, 137, 3996-4009.

In an alternative process, compounds of formula IIIc can be obtainedfrom compounds of the formula XXII wherein R₃, R_(4a), R_(5a), andR_(5b) are as described in formula I, following the synthesis describedin Scheme 10:

Amines of formula IIIc may be obtained from intermediates of formulaXXII, wherein R₃, R_(4a), R_(5a), and R_(5b) are as described in formulaI and Z₃ is NPhth or NBoc₂. Such intermediates can be obtained fromalcohols of formula XXI by a Mitsunobu reaction, which involves treatingalcohols of formula XXI with diisopropyl azodicarboxylate in thepresence of a phosphine such as triphenylphosphine or tributylphosphineand of an amine such as phthalimide or bis(tert-butoxycarbonyl)amine.Mitsunobu reactions are known by those skilled in the art to proceedwith inversion of the stereocenter, as described for instance in Chem.Rev. 2009, 109, 2551-2651. Amines of formula XXII can then betransformed into amines of formula IIIc by treatment with hydrazine ifZ₃=NPhth or with acid, for example trifluoroacetic acid, if Z₃=NBoc₂.

Alternatively, amines of formula IIIc may be obtained by reduction ofazides of formula XXIII, wherein R₃, R_(4a), R_(5a), and R_(5b) are asdescribed in formula I, by treatment with triphenylphosphine and water(Staudinger reaction) or by hydrogenation for example using a palladiumcatalyst in the presence of hydrogen. Azides of formula XXIII may beobtained by treatment of alcohols of formula XXI, wherein R₃, R_(4a),R_(5a), and R_(5b) are as described in formula I, with an azidationreagent such as diphenyl phosphoryl azide in a solvent such as tolueneor THE in presence of a base such as DBU. Such processes are known bythose skilled in the art to proceed with inversion of the stereocenterand are described in the literature for instance in Adv. Synth. Catal.2018, 360, 2157-2165.

Alcohols of formula XXI may be obtained by enantioselective reduction ofketones of formula XXIV, wherein R₃, R_(4a), R_(5a), and R_(5b) are asdescribed in formula I. Such reductions can be done using a catalyst,for instance a ruthenium or a rhodium catalyst with a chiral ligand suchas RuCl[(R,R)-TsDPEN](mesitylene) or RuBF₄[(R,R)-TsDPEN](p-cymene) inthe presence of a hydrogen donor system such as for example HCOOH/Et₃Nor HCO₂NH₄. Such processes are described in the literature for instancein J. Org. Chem. 2017, 82, 5607.

Alternatively, compounds of formula IIIc may also be prepared asoutlined in Scheme 11.

Amines of formula IIIc can be prepared by deprotection of amines offormula XXV, wherein R₃, R_(4a), R_(5a), and R_(5b) are as described informula I, for instance using an acid such as trifluoroacetic acid orhydrochloric acid. Amines of formula XXV can be obtained by condensationof diamines of formula XXVII, wherein R_(5a), and R_(5b) are asdescribed in formula I, on diketones of formula XXVI, wherein R₃, andR_(4a) are as described in formula I. This condensation can take placein the presence of a suitable solvent such as ethanol or isopropanol inpresence of an oxidant such as air or DDQ. Diketones of formula XXVI maybe formed by oxidation of hydroxyketones of formula XXVII wherein R₃,and R_(4a) are as described in formula I. This oxidation can involve forinstance SO₃-pyridine in presence of DMSO and a base for instancetriethylamine or alternatively sodium hypochlorite in presence of acatalyst such as TEMPO/Bu₄NHSO₄. Examples of such oxidations can befound in the literature, for instance in Synlett, 2014, 25, 596 or J.Am. Chem. Soc. 1990, 112, 5290-5313. Hydroxyketones of formula XXVII maybe synthesized by cross-benzoin condensation between aldehydes offormula XXIX, wherein R_(4a) is as described in formula I, and aldehydesof formula XXVIII, wherein R₃ is as described in formula I. Aldehydes offormula XXVIII are commercially available in chiral form, like forinstance Boc-L-alaninal (CAS 79069-50-4) or tert-butylN-[(1S)-1-(cyclopropylmethyl)-2-oxo-ethyl]carbamate (CAS 881902-36-9).Cross-benzoin condensations are done in the usual way by employing anorganocatalyst such as a triazolium salt or a thiazolium salt in thepresence of a base such as potassium tert-butoxide orisopropyldiethylamine in a suitable solvent such as DCM or THE at atemperature between −20° C. and the boiling point of the solvent.Examples of catalysts for such transformations have been described inthe literature for instance in J. Am. Chem. Soc. 2014, 136, 7539-7542 orin Org. Lett. 2016, 18, 4518-4521.

As shown in Scheme 12, compounds of formula Id can be alternativelyprepared by reaction of compounds of formula XXX (wherein A₁, A₂, A₃,A₄, A₅, R₁, R_(2a), R_(2b), R₃, R_(5a), and R_(5b) are as defined informula I and X₀₇ is a leaving group like, for example, chlorine,bromine, iodine) with compounds of formula XXXI (Stille reaction) orcompounds of formula XXXII (Suzuki-Miyaura reaction) in the presence ofa palladium catalyst as described in detail in Scheme 7.

Compounds of formula XXX can be prepared by coupling of amines offormula XXXIII and compounds of formula II, wherein A₁, A₂, A₃, A₄, A₅,R_(2a), R_(2b) and X₁ are described in Scheme 1, under the conditionsdescribed in detail in Scheme 1. Under the same conditions, if R₁═H,compounds of formula XXX may be obtained directly from compounds offormula XXXIV.

Compounds of formula XXXIII can be prepared by treatment of compounds offormula XXXIV, with compounds of formula XXXV (wherein R₁ is as definedin formula I), e.g. in the presence of NaBH(OAc)₃ or NaBH₃CN, in asuitable solvent, preferably in acetic acid at room temperature analogto WO2002/088073, page 35. Alternatively, another reagent system for thereductive amination uses a combination of Ti(i-OiPr)₄ and NaBH₄ (seeSynthesis 2003 (14), 2206).

Amines of formula XXXIV can be prepared by deracemization proceduremethod, which involves for example, a selective acylation of oneenantiomer. Such an example is described more in details in Scheme 13.

Amines of formula XXXIV may be obtained by biocatalyzed deracemizationof amines of formula XXXIVa, wherein R₃, R_(5a), and R_(5b) are as informula 1 and X₀₇ is a leaving group such as bromine, chlorine oriodine. This may be done for instance using a lipase, e.g. CandidaAntarctica lipase B or Pseudomonas fluorescens lipase, eventually inimmobilized form (e.g. Novozym® 435) in presence of an acyl donor, e.g.ethyl methoxyacetate or vinyl acetate, in a suitable solvent such asacetonitrile or methyl tert-butyl ether at temperatures between 20° C.to 100° C. Such processes are described for instance in J. Org. Chem.2007, 72, 6918-6923 or Adv. Synth. Catal. 2007, 349, 1481-1488. Theexpected stereochemical outcome of such enzymatic deracemization areknown of those skilled in the art and are documented in the literature,for instance in J. Org. Chem. 1991, 56, 2656-2665 or J. Am. Chem. Soc.2015, 137, 3996-4009.

Alternatively, resolution of amines of formula XXXIVa to give amines offormula XXXIV may be achieved using a chiral auxiliary, as described inScheme 14.

Amines of formula XXXIV can be prepared from intermediates of formulaXXXVII, wherein R₃, R_(5a), and R_(5b) are as in compounds of theformula 1, X₀₇ is a leaving group such as bromine, chlorine or iodine,and X₁₂* is a chiral auxiliary, by treatment with acids such as HCl orbases such as NaOH. Chiral auxiliaries of formula LII are for instancemandelic acid or (1R)-menthylchloroformate. Intermediates of formulaXXXVII can be formed by coupling of a chiral auxiliary of formula XXXVI,wherein X₀ is a leaving group, such as chlorine, with amines of theformula XXXIVa following the conditions detailed in Scheme 1. Examplesof such deracemization processes are reported in the literature, forinstance in J. Org. Chem. 2007, 72, 485-493.

Alternatively, amines of formula XXXIV can be formed as described inScheme 15.

Alternatively, amines of formula XXXIV may be obtained fromintermediates of formula XXIIa, wherein R₃, R_(5a), and R_(5b) are asdescribed in formula I, X₀₇ is a leaving group such as a halogen orsulfonate, for instance bromide, and Z₃ is NPhth or NBoc₂. Suchintermediates can be obtained from alcohols of formula XXIa, wherein R₃,R_(5a), and R_(5b) are as described in formula I and X₀₇ is a leavinggroup, by a Mitsunobu reaction, which involves treating alcohols offormula XXIa with diisopropyl azodicarboxylate in the presence of aphosphine such as triphenylphosphine or tributylphosphine and of anamine such as phthalimide or bis(tert-butoxycarbonyl)amine. Mitsunobureactions are known by those skilled in the art to proceed withinversion of the stereocenter, as described for instance in Chem. Rev.2009, 109, 2551-2651. Amines of formula LIII can then be transformedinto amines of formula IId by treatment with hydrazine if Z₃=NPhth orwith TFA if Z₃=NBoc₂.

Alternatively, amines of formula XXXIV may be obtained by reduction ofazides of formula XXIIIa, wherein R₃, R_(5a), and R_(5b) are asdescribed in formula I and X₀₇ is a leaving group such as a halogen orsulfonate, for instance bromide, by treatment with triphenylphosphineand water (Staudinger reaction) or by hydrogenation for example using apalladium catalyst in the presence of hydrogen. Azides of formula XXIIIamay be obtained by treatment of alcohols of formula XXIa with anazidation reagent such as diphenyl phosphoryl azide in a solvent such astoluene or THE in presence of a base such as DBU. Such processes areknown by those skilled in the art to proceed with inversion of thestereocenter and are described in the literature for instance in Adv.Synth. Catal. 2018, 360, 2157-2165.

Alcohols of formula XXIa may be obtained by enantioselective reductionof ketones of formula XXIVa, wherein R₃, R_(5a), and R_(5b) are asdescribed in formula I and X₀₇ is a leaving group such as a halogen orsulfonate, for instance bromide. Such reductions can be done usingcatalysts, for instance a ruthenium or a rhodium catalyst with a chiralligand such as RuCl[(R,R)-TsDPEN](mesitylene) orRuBF₄[(R,R)-TsDPEN](p-cymene) in the presence of a hydrogen donor systemsuch as for example HCOOH/Et₃N or HCO₂NH₄. Such processes are describedin the literature for instance in J. Org. Chem. 2017, 82, 5607.

Compounds of Formula II

wherein X1 is a leaving group, such as a halogen or sulfonate, forinstance chloride, can be made, for example, as shown in Schemes 16-18.

Compounds of formula IIa wherein R_(2a), R_(2b), A₄ and A₅ are asdescribed in formula I, can be prepared according to reaction scheme 16.Compounds of formula XLII are either known, or they can be prepared bymethods known to a person skilled in the art. For example, a compound offormula XL is reacted with an electrophilic iodinating reagent, such asN-iodosuccinimide, in a solvent, such as hexafluoroisopropanol, asdescribed for example in J. Org. Chem. 2018, 83, 930, to obtaincompounds of formula XLI. Cyanation of compounds of formula XLI withcopper(I) cyanide in a solvent, such as DMF, at temperatures such as100° C., provides compounds of formula XLII (procedure analog toWO2005/100298, page 44). Treatment of compounds of formula XLII withformic acid and sulfuric acid at temperatures between 80 and 100° C.,provides compounds of formula XLIII (procedure analog to WO2018/206539,page 80). Subsequent conversion to compounds of formula IIa isaccomplished via according to methods known to the person skilled in theart, for example with thionyl chloride in presence of catalyticN,N-dimethylformamide at reflux, analog to WO2015/54572, page 263.

Compounds of formula IIb wherein R_(2a), R_(2b), A₄ and A₅ are asdescribed in formula I, can be prepared according to reaction scheme 17.A compound of formula XLII, prepared as in Scheme 16, is reacted withchlorosulfonyl isocyanate, then further reacted with water at reflux, asdescribed for example in Synth. Commun. 1988, 18, 525, to provideintermediates of formula XLIV. Subsequent conversion of intermediates offormula XLIV to compounds of formula IIa is accomplished usingchlorinating reagents, such as POCl₃, optionally in the presence ofbase, such as N,N-diisopropylethylamine. These chlorinating methods arewell known to the person skilled in the art.

Compounds of formula IIc wherein R_(2a), R_(2b), A₄ and A₅ are asdescribed in formula I, can be prepared according to reaction scheme 18,analog to procedures found in ChemCatChem 2017, 10, 965. Meldrum's acidis converted to compound XLV by refluxing in trimethyl orthoformate andfurther converted to compounds of formula XLVI in the same pot byaddition of anilines of formula XL. Compounds of formula XLVI arerefluxed in diphenyl ether to obtain 4-hydroxyquinolines of formulaXLVII. Compounds of formula IIc are then obtained via chlorination ofcompounds of formula XLVII using chlorinating reagents, such as POCl₃,well known to the person skilled in the art.

Compounds of Formula IVc

can be made, for example, as shown in Scheme 19.

Compounds of formula IVc wherein Z is H, C₁-C₃ alkyl, cyclopropyl, CF₃,R2a, R2b, A4 and A5 are as described in formula I, can be preparedaccording to reaction scheme 20. Compounds of formula XLII, prepared asin Scheme 16, are reacted in the presence of compounds of formula XLVIIIat elevated temperatures, such as 180° C., as described for example inEur. J. Med. Chem. 2017, 141, 446, to provide amines of formula IVc.

Alternatively, compounds of the formula Iab can be made, for example, asshown in Scheme 20.

Compounds of formula Iab, wherein R1, R2a, R2b, R3, A4, A5, Q are asdescribed in formula I, can be prepared according to scheme 21, analogto the procedures in WO2010/093419, page 225. Compounds of formula XLII,prepared as in Scheme 16, are treated with N,N-dimethylformamidedimethyl acetal at elevated temperature, preferably 90° C., to provideformamidine products of formula XLVIII. Reaction with amines of formulaIII at elevated temperature, preferably 120° C., in a suitable solvent,preferably acetic acid, provides compounds of formula Iab.

Compounds of the Formula If

can be made, for example, as shown in Scheme 21.

Compounds of formula If, wherein R1, R2a, R2b, R3, A4, A5, Q are asdescribed in formula I, can be prepared according to Scheme 21. Reactionof compounds of formula IIb, prepared as in Scheme 17, with amines offormula III, using procedures presented in Scheme 1, provides compoundsof formula Ie. Treatment of compounds of formula Ie under acidicconditions, preferably with acetic acid, at elevated temperatures,preferably between 70 and 80° C., as described in Heterocycles 1996, 43,2607, provides intermediates of formula LI. Methylation of compounds offormula LI to obtain compounds of formula If can be achieved using anelectrophilic methyl sources, such as dimethyl sulfate or methyl iodide,in the presence of a base, such potassium carbonate or sodium hydride,as well known to the person skilled in the art.

Compounds of the Formula Ig

can be made, for example, as shown in Scheme 22.

Compounds of formula Ig, wherein R1, R2a, R2b, R3, A4, A5, Q are asdescribed in formula I, can be prepared according to Scheme 22. Acompound of formula XLII, as prepared in Scheme 16, is treated with adiazotizing reagent, preferably isoamylnitrite, in diiodomethanesolvent, at elevated temperature, preferably 80° C., as described in J.Org. Chem. 1990, 55, 2543, to provide intermediates of formula LX.Reduction of compounds of formula LX is achieved in the presence of aselective reductant, such as diisobutylaluminum hydride (DIBALH), in asolvent, such as toluene, at low temperatures, preferably −78° C., andgives a compound of formula LXI. Subsequent Sonogashira coupling in thepresence of suitable palladium and copper catalysts, preferablybis(triphenylphosphine)palladium chloride and copper(I) iodide, withtrimethylsilylacetylene, in a solvent, such as triethylamine, givescompounds of formula LXII. Cyclization with ammonia in methanol givescompounds of formula LXIII. Procedures are analog to those described forexample in Eur. J. Med. Chem. 2016, 118, 170. Treatment of compounds offormula LXIII with an oxidant, such as 3-chloro-benzenecarboperoxoicacid or hydrogen peroxide, in a solvent, preferably dichloromethane,gives N-oxides of formula LXIV. Such oxidations are well known to theperson skilled in the art. Coupling of compounds of formula LXIV withamines of formula III in the presence of a suitable activator, such asbromotripyrrolidinophosphonium hexafluorophosphate (PyBroP®),potentially in the presence of base, such as N,N-diisopropylethylamine,analog to procedure described in WO2016/123627, page 87, gives compoundsof formula Ig.

Compounds of Formula IId

wherein X1 is a leaving group, such as a halogen or sulfonate, forinstance chloride, can be made, for example, as shown in Scheme 23.

Compounds of formula IId, wherein R2a, R2b, A4, A5 are as described informula I, can be prepared according to Scheme 23. A compound of formulaXLI, as prepared in Scheme 16, is treated with a palladium catalyst,preferably Pd(PPh₃)₄, along with tributyl(1-ethoxyvinyl)tin, at elevatedtemperature, preferably 105° C., as described in EP1782811, page 57, toprovide intermediates of formula LXV. Treatment of compounds of formulaLXV with aqueous sodium nitrite in the presence of acids, such ashydrochloric acid or a sulfuric acid/acetic acid mixture at lowtemperatures, preferably between 0 and 5° C., analog to Bioorg. Med.Chem. Lett., 25, 919, gives compounds of formula LXVI. Compounds offormula IId are then obtained via chlorination of compounds of formulaLXVI using chlorinating reagents, such as POCl₃, optionally in thepresence of an amine base, such as N,N-diisopropylethylamine, well knownto the person skilled in the art.

Compounds of Formula IIe

wherein X1 is a leaving group, such as a halogen or sulfonate, forinstance chloride, can be made, for example, as shown in Scheme 24.

Compounds of formula IIe, wherein R2a, R2b, A4, A5 are as described informula I, can be prepared according to Scheme 24. A compound of formulaXL is heated with ethyl 2-cyano-3-ethoxyacrylate at elevatedtemperature, preferably 140° C., as described in Tetrahedron Letters,2015, 56, 5112, to provide intermediates of formula LXVII. Heating ofcompounds of formula LXVII at elevated temperatures, preferably betweenat 260° C., in a solvent, preferably diphenyl ether or diphenylether-biphenyl eutectic mixture (Dowtherm A®), gives compounds offormula LXVIII. Subsequent conversion to compounds of formula IIe isaccomplished via according to methods known to the person skilled in theart, for example with thionyl chloride in presence of catalyticN,N-dimethylformamide at reflux, analog to US2003/212276, page 15.

Compounds of the Formula Ih

can be made, for example, as shown in Scheme 25.

Compounds of formula Ih, wherein R1, R2a, R2b, R3, A4, A5, Q are asdescribed in formula I, can be prepared according to Scheme 25. Acompound of formula XLII, as prepared in Scheme 16, is treated withhydrogen peroxide, either as an aqueous solution or as an urea adduct,in methanol-water solvent, in the presence of base, preferably potassiumcarbonate, analog to WO2011/4276, page 132, to provide intermediates offormula LXX. Treatment of compounds of formula LXX with aqueous sodiumnitrite in the presence of acids, such as hydrochloric acid or asulfuric acid/acetic acid mixture at low temperatures, preferablybetween 0 and 5° C., analog to US2014/0275072, paragraph 133, givescompounds of formula LXXI. Coupling of compounds of formula LXXI withamines of formula III in the presence of a suitable activator, such as(benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate(PyBoP®), in the presence of base, such as N,N-diisopropylethylamine,analog to procedure described in WO2014/085528, page 55, gives compoundsof formula Ih.

Compounds of the Formula II

can be made, for example, as shown in Scheme 26.

Scheme 26:

Compounds of formula Ii, wherein R1, R2a, R2b, R3, A4, A5, Q are asdescribed in formula I, can be prepared according to Scheme 26. Acompound of formula Iaa, as prepared in Scheme 1, 5 or 6, is treatedwith a fluorinating reagent, preferably1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octanebis(tetrafluoroborate) (Selectfluor), in a solvent, preferablyacetonitrile, analog to WO2018/34917, page 91, to provide compounds offormula Ii.

Compounds of the Formula Ij

can be made, for example, as shown in Scheme 27.

Compounds of formula Ij, wherein R1, R2a, R2b, R3, A4, A5, Q are asdescribed in formula I, can be prepared according to Scheme 27. Acompound of formula Iaa, as prepared in Scheme 1, 5 or 6, is treatedwith a chlorinating reagent, preferably N-chlorosuccinimide, in thepresence of catalytic dimethyl sulfoxide (DMSO), in a solvent,preferably dichloromethane, analog to Nature Catalysis, 2020, 3, 107, toprovide compounds of formula Ij.

Compounds of the Formula Im

can be made, for example, as shown in Scheme 28.

Compounds of formula Im, wherein R1, R2a, R2b, R3, A1, A2, A3, A4, A5are as described in formula I, can be prepared according to Scheme 28. Acompound of formula Ik, as prepared in Scheme 1, 3, 5, 6, 20, 21, 22,25, 26, or 27, is treated with ammonium sulfide, in a solvent,preferably pyridine, optionally in the presence of a base, preferablytriethylamine, analog to WO2017/192385 page 60, to provide compounds offormula Im.

Compounds of the Formula In

can be made, for example, as shown in Scheme 29.

Compounds of formula In, wherein R1, R2a, R2b, R3, A1, A2, A3, A4, A5are as described in formula I, can be prepared according to Scheme 29. Acompound of formula Im, as prepared in Scheme 28, is reacted with3-bromo-1,1,1-trifluoroacetone, in a solvent, preferablyN,N-dimethylformamide or acetonitrile, analog to WO2010/136817, page110, to provide compounds of formula LXXII. Treatment of compounds offormula LXXII with trifluoroacetic anhydride, in the presence of base,preferably triethylamine, in a solvent, preferably tetrahydrofuran oracetonitrile, analog to J. Med. Chem., 2013, 56, 8712, gives compoundsof formula In.

Depending on the procedure or the reaction conditions, the reactants canbe reacted in the presence of a base. Examples of suitable bases arealkali metal or alkaline earth metal hydroxides, alkali metal oralkaline earth metal hydrides, alkali metal or alkaline earth metalamides, alkali metal or alkaline earth metal alkoxides, alkali metal oralkaline earth metal acetates, alkali metal or alkaline earth metalcarbonates, alkali metal or alkaline earth metal dialkylamides or alkalimetal or alkaline earth metal alkylsilylamides, alkylamines,alkylenediamines, free or N-alkylated saturated or unsaturatedcycloalkylamines, basic heterocycles, ammonium hydroxides andcarbocyclic amines. Examples which may be mentioned are sodiumhydroxide, sodium hydride, sodium amide, sodium methoxide, sodiumacetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide,potassium carbonate, potassium hydride, lithium diisopropylamide,potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine,diisopropylethylamine, triethylenediamine, cyclohexylamine,N-cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine,4-(N,N-dimethylamino)pyridine, quinuclidine, N-methylmorpholine,benzyltrimethylammonium hydroxide and 1,8-diazabicyclo[5.4.0]undec-7-ene(DBU).

The reactants can be reacted with each other as such, i.e. withoutadding a solvent or diluent. In most cases, however, it is advantageousto add an inert solvent or diluent or a mixture of these. If thereaction is carried out in the presence of a base, bases which areemployed in excess, such as triethylamine, pyridine, N-methylmorpholineor N,N-diethylaniline, may also act as solvents or diluents.

The reactions are advantageously carried out in a temperature range fromapproximately −80° C. to approximately +140° C., preferably fromapproximately −30° C. to approximately +100° C., in many cases in therange between ambient temperature and approximately +80° C.

Depending on the choice of the reaction conditions and startingmaterials which are suitable in each case, it is possible, for example,in one reaction step only to replace one substituent by anothersubstituent according to the invention, or a plurality of substituentscan be replaced by other substituents according to the invention in thesame reaction step.

Salts of compounds of formula I can be prepared in a manner known perse. Thus, for example, acid addition salts of compounds of formula I areobtained by treatment with a suitable acid or a suitable ion exchangerreagent and salts with bases are obtained by treatment with a suitablebase or with a suitable ion exchanger reagent.

Salts of compounds of formula I can be converted in the customary mannerinto the free compounds I, acid addition salts, for example, bytreatment with a suitable basic compound or with a suitable ionexchanger reagent and salts with bases, for example, by treatment with asuitable acid or with a suitable ion exchanger reagent.

Salts of compounds of formula I can be converted in a manner known perse into other salts of compounds of formula I, acid addition salts, forexample, into other acid addition salts, for example by treatment of asalt of inorganic acid such as hydrochloride with a suitable metal saltsuch as a sodium, barium or silver salt, of an acid, for example withsilver acetate, in a suitable solvent in which an inorganic salt whichforms, for example silver chloride, is insoluble and thus precipitatesfrom the reaction mixture.

Depending on the procedure or the reaction conditions, the compounds offormula I, which have salt-forming properties can be obtained in freeform or in the form of salts.

The compounds of formula I and, where appropriate, the tautomersthereof, in each case in free form or in salt form, can be present inthe form of one of the isomers which are possible or as a mixture ofthese, for example in the form of pure isomers, such as antipodes and/ordiastereomers, or as isomer mixtures, such as enantiomer mixtures, forexample racemates, diastereomer mixtures or racemate mixtures, dependingon the number, absolute and relative configuration of asymmetric carbonatoms which occur in the molecule and/or depending on the configurationof non-aromatic double bonds which occur in the molecule; the inventionrelates to the pure isomers and also to all isomer mixtures which arepossible and is to be understood in each case in this sense hereinaboveand hereinbelow, even when stereochemical details are not mentionedspecifically in each case.

Diastereomer mixtures or racemate mixtures of compounds of formula I, infree form or in salt form, which can be obtained depending on whichstarting materials and procedures have been chosen can be separated in aknown manner into the pure diasteromers or racemates on the basis of thephysicochemical differences of the components, for example by fractionalcrystallization, distillation and/or chromatography.

Enantiomer mixtures, such as racemates, which can be obtained in asimilar manner can be resolved into the optical antipodes by knownmethods, for example by recrystallization from an optically activesolvent, by chromatography on chiral adsorbents, for examplehigh-performance liquid chromatography (HPLC) on acetyl cellulose, withthe aid of suitable microorganisms, by cleavage with specific,immobilized enzymes, via the formation of inclusion compounds, forexample using chiral crown ethers, where only one enantiomer iscomplexed, or by conversion into diastereomeric salts, for example byreacting a basic end-product racemate with an optically active acid,such as a carboxylic acid, for example camphor, tartaric or malic acid,or sulfonic acid, for example camphorsulfonic acid, and separating thediastereomer mixture which can be obtained in this manner, for exampleby fractional crystallization based on their differing solubilities, togive the diastereomers, from which the desired enantiomer can be setfree by the action of suitable agents, for example basic agents.

Pure diastereomers or enantiomers can be obtained according to theinvention not only by separating suitable isomer mixtures, but also bygenerally known methods of diastereoselective or enantioselectivesynthesis, for example by carrying out the process according to theinvention with starting materials of a suitable stereochemistry.

N-oxides can be prepared by reacting a compound of the formula I with asuitable oxidizing agent, for example the H₂O₂/urea adduct in thepresence of an acid anhydride, e.g. trifluoroacetic anhydride. Suchoxidations are known from the literature, for example from J. Med.Chem., 32 (12), 2561-73, 1989 or WO 2000/15615.

It is advantageous to isolate or synthesize in each case thebiologically more effective isomer, for example enantiomer ordiastereomer, or isomer mixture, for example enantiomer mixture ordiastereomer mixture, if the individual components have a differentbiological activity.

The compounds of formula I and, where appropriate, the tautomersthereof, in each case in free form or in salt form, can, if appropriate,also be obtained in the form of hydrates and/or include other solvents,for example those which may have been used for the crystallization ofcompounds which are present in solid form.

The compounds of formula I according to the following Tables D-1 to D-66can be prepared according to the methods described above. The exampleswhich follow are intended to illustrate the invention and show preferredcompounds of formula I, in the form of a compound of formula I-D.

Table D-1 provides 12 compounds D-1.001 to D-1.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is Cl, R_(2b) is Cl, and Q is as defined in table Z. For example,D-1.002 is

Table D-2 provides 12 compounds D-2.001 to D-2.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is Cl, R_(2b) is C, and Q is as defined in table Z.

Table D-3 provides 12 compounds D-3.001 to D-3.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is Cl, R_(2b) is C, and Q is as defined in tableZ.

Table D-4 provides 12 compounds D-4.001 to D-4.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is Cl, R_(2b) is C, and Q is as defined in table Z.

Table D-5 provides 12 compounds D-5.001 to D-5.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is Cl, R_(2b) is C, and Q is as defined in table Z.

Table D-6 provides 12 compounds D-6.001 to D-6.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is Cl, R_(2b) is C, and Q is as defined in tableZ.

Table D-7 provides 12 compounds D-7.001 to D-7.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is CF₃, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-8 provides 12 compounds D-8.001 to D-8.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is CF₃, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-9 provides 12 compounds D-9.001 to D-9.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ isCH2-cyclopropyl, R_(2a) is CF₃, R_(2b) is CF₃, and Q is as defined intable Z.

Table D-10 provides 12 compounds D-10.001 to D-10.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is CF₃, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-11 provides 12 compounds D-11.001 to D-11.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is CF₃, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-12 provides 12 compounds D-12.001 to D-12.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is CF₃, R_(2b) is CF₃, and Q is as defined intable Z.

Table D-13 provides 12 compounds D-13.001 to D-13.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is CF₃, R_(2b) is C, and Q is as defined in table Z.

Table D-14 provides 12 compounds D-14.001 to D-14.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is CF₃, R_(2b) is C, and Q is as defined in table Z.

Table D-15 provides 12 compounds D-15.001 to D-15.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is CF₃, R_(2b) is C, and Q is as defined intable Z.

Table D-16 provides 12 compounds D-16.001 to D-16.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is CF₃, R_(2b) is C, and Q is as defined in table Z.

Table D-17 provides 12 compounds D-17.001 to D-17.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is CF₃, R_(2b) is C, and Q is as defined in table Z.

Table D-18 provides 12 compounds D-18.001 to D-18.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is CF₃, R_(2b) is C, and Q is as defined intable Z.

Table D-19 provides 12 compounds D-19.001 to D-19.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is Cl, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-20 provides 12 compounds D-20.001 to D-20.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is Cl, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-21 provides 12 compounds D-21.001 to D-21.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is Cl, R_(2b) is CF₃, and Q is as defined intable Z.

Table D-22 provides 12 compounds D-22.001 to D-22.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is Cl, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-23 provides 12 compounds D-23.001 to D-23.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is Cl, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-24 provides 12 compounds D-24.001 to D-24.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is Cl, R_(2b) is CF₃, and Q is as defined intable Z.

Table D-25 provides 12 compounds D-25.001 to D-25.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is Cl, R_(2b) is Br, and Q is as defined in table Z.

Table D-26 provides 12 compounds D-26.001 to D-26.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is Cl, R_(2b) is Br, and Q is as defined in table Z.

Table D-27 provides 12 compounds D-27.001 to D-27.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is Cl, R_(2b) is Br, and Q is as defined intable Z.

Table D-28 provides 12 compounds D-28.001 to D-28.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is Cl, R_(2b) is Br, and Q is as defined in table Z.

Table D-29 provides 12 compounds D-29.001 to D-29.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is Cl, R_(2b) is Br, and Q is as defined in table Z.

Table D-30 provides 12 compounds D-30.001 to D-30.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is Cl, R_(2b) is Br, and Q is as defined intable Z.

Table D-31 provides 12 compounds D-31.001 to D-31.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is Br, R_(2b) is C, and Q is as defined in table Z.

Table D-32 provides 12 compounds D-32.001 to D-32.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is Br, R_(2b) is C, and Q is as defined in table Z.

Table D-33 provides 12 compounds D-33.001 to D-33.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is Br, R_(2b) is C, and Q is as defined in tableZ.

Table D-34 provides 12 compounds D-34.001 to D-34.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is Br, R_(2b) is C, and Q is as defined in table Z.

Table D-35 provides 12 compounds D-35.001 to D-35.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is Br, R_(2b) is Cl, and Q is as defined in table Z.

Table D-36 provides 12 compounds D-36.001 to D-36.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is Br, R_(2b) is Cl, and Q is as defined intable Z.

Table D-37 provides 12 compounds D-37.001 to D-37.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is CF₃, R_(2b) is Br, and Q is as defined in table Z.

Table D-38 provides 12 compounds D-38.001 to D-38.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is CF₃, R_(2b) is Br, and Q is as defined in table Z.

Table D-39 provides 12 compounds D-39.001 to D-39.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is CF₃, R_(2b) is Br, and Q is as defined intable Z.

Table D-40 provides 12 compounds D-40.001 to D-40.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is CF₃, R_(2b) is Br, and Q is as defined in table Z.

Table D-41 provides 12 compounds D-41.001 to D-41.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is CF₃, R_(2b) is Br, and Q is as defined in table Z.

Table D-42 provides 12 compounds D-42.001 to D-42.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is CF₃, R_(2b) is Br, and Q is as defined intable Z.

Table D-43 provides 12 compounds D-43.001 to D-43.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is Br, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-44 provides 12 compounds D-44.001 to D-44.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is Br, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-45 provides 12 compounds D-45.001 to D-45.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is Br, R_(2b) is CF₃, and Q is as defined intable Z.

Table D-46 provides 12 compounds D-46.001 to D-46.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is Br, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-47 provides 12 compounds D-47.001 to D-47.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is Br, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-48 provides 12 compounds D-48.001 to D-48.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is Br, R_(2b) is CF₃, and Q is as defined intable Z.

Table D-49 provides 12 compounds D-49.001 to D-49.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is Br, R_(2b) is Br, and Q is as defined in table Z.

Table D-50 provides 12 compounds D-50.001 to D-50.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is Br, R_(2b) is Br, and Q is as defined in table Z.

Table D-51 provides 12 compounds D-51.001 to D-51.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is Br, R_(2b) is Br, and Q is as defined intable Z.

Table D-52 provides 12 compounds D-52.001 to D-52.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is Br, R_(2b) is Br, and Q is as defined in table Z.

Table D-53 provides 12 compounds D-53.001 to D-53.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is Br, R_(2b) is Br, and Q is as defined in table Z.

Table D-54 provides 12 compounds D-54.001 to D-54.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is Br, R_(2b) is Br, and Q is as defined intable Z.

Table D-55 provides 12 compounds D-55.001 to D-55.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is CF₃, R_(2b) is I, and Q is as defined in table Z.

Table D-56 provides 12 compounds D-56.001 to D-56.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is CF₃, R_(2b) is I, and Q is as defined in table Z.

Table D-57 provides 12 compounds D-57.001 to D-57.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is CF₃, R_(2b) is I, and Q is as defined intable Z.

Table D-58 provides 12 compounds D-58.001 to D-58.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is CF₃, R_(2b) is I, and Q is as defined in table Z.

Table D-59 provides 12 compounds D-59.001 to D-59.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is CF₃, R_(2b) is I, and Q is as defined in table Z.

Table D-60 provides 12 compounds D-60.001 to D-60.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is CF₃, R_(2b) is I, and Q is as defined intable Z.

Table D-61 provides 12 compounds D-61.001 to D-61.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is I, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-62 provides 12 compounds D-62.001 to D-62.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is I, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-63 provides 12 compounds D-63.001 to D-63.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is CH, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is 1, R_(2b) is CF₃, and Q is as defined intable Z.

Table D-64 provides 12 compounds D-64.001 to D-64.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is H, R_(2a)is I, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-65 provides 12 compounds D-65.001 to D-65.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ is CH₃,R_(2a) is I, R_(2b) is CF₃, and Q is as defined in table Z.

Table D-66 provides 12 compounds D-66.001 to D-66.012 of formula I-Dwherein A₁ is N, A₂ is CH, A₃ is N, A₄ is CH, A₅ is CH, R₁ isCH₂-cyclopropyl, R_(2a) is I, R_(2b) is CF₃, and Q is as defined intable Z.

TABLE Z Substituent definitions of Q: Index Q 1

2

3

4

5

6

7

8

9

10

11

12

Also made available are certain intermediate compounds of formulaeII(i), III(i), IV(i), V(i), VII(i), XI(i), and XIV(i), some of which arenovel. For example,

-   -   A compound of formula II(i), wherein (i) X1 is Cl and A₁, A₂,        A₃, A₄, As, R_(2a) and R_(2b) are as defined in any one Tables        D-1 to D-66; (ii) wherein (i) X1 is Br and A₁, A₂, A₃, A₄, As,        R_(2a) and R_(2b) are as defined in any one Tables D-1 to D-66.

-   -   A compound of formula III(i), wherein (i) R₁ is H and Q is as        defined in table Z; (ii) wherein (i) R₁ is CH₃ and Q is as        defined in table Z; and (iii) wherein (i) R₁ is CH₂-cyclopropyl        and Q is as defined in table Z.

-   -   A compound of formula IV(i), wherein A₁, A₂, A₃, A₄, As, R_(2a)        and R_(2b) are as defined in any one Tables D-1 to D-66.

-   -   A compound of formula V(i), wherein (i) X2 is Cl and Q is as        defined in table Z; (ii) wherein (i) X2 is Br and Q is as        defined in table Z; and (iii) wherein (i) X2 is I and Q is as        defined in table Z.

-   -   A compound of formula VII(i), wherein Q is as defined in table        Z.

-   -   A compound of formula XI(i), wherein A₁, A₂, A₃, A₄, As, R₁,        R_(2a) and R_(2b) are as defined in any one Tables D-1 to D-66.

-   -   A compound of formula XIV(i), wherein A₁, A₂, A₃, A₄, As, R₁,        R_(2a) and R_(2b) are as defined in any one Tables D-1 to D-66.

In further aspect, the present invention accordingly makes availablecompounds of formulae II(i), III(i), IV(i), V(i), VII(i), XI(i), andXIV(i), wherein in each case, as applicable, A₁, A₂, A₃, A₄, As, R₁,R_(2a) and R_(2b) and Q are as defined for formula I in the firstaspect; and in respect of formula II(i), X1 is a halogen, preferablychloro or bromo. Furthermore, the corresponding embodiments illustratedfor formula I also apply to the compounds of formulae II(i), III(i),IV(i), V(i), VII(i), XI(i), and XIV(i), The compounds of formula Iaccording to the invention are preventively and/or curatively valuableactive ingredients in the field of pest control, even at low rates ofapplication, which have a very favorable biocidal spectrum and are welltolerated by warm-blooded species, fish and plants. The activeingredients according to the invention act against all or individualdevelopmental stages of normally sensitive, but also resistant, animalpests, such as insects or representatives of the order Acarina. Theinsecticidal or acaricidal activity of the active ingredients accordingto the invention can manifest itself directly, i. e. in destruction ofthe pests, which takes place either immediately or only after some timehas elapsed, for example during ecdysis, or indirectly, for example in areduced oviposition and/or hatching rate.

Examples of the above mentioned animal pests are:

from the order Acarina, for example,

Acalitus spp, Aculus spp, Acaricalus spp, Aceria spp, Acarus siro,Amblyomma spp., Argas spp., Boophilus spp., Brevipalpus spp., Bryobiaspp, Calipitrimerus spp., Chorioptes spp., Dermanyssus gallinae,Dermatophagoides spp, Eotetranychus spp, Eriophyes spp., Hemitarsonemusspp, Hyalomma spp., Ixodes spp., Olygonychus spp, Ornithodoros spp.,Polyphagotarsone latus, Panonychus spp., Phyllocoptruta oleivora,Phytonemus spp, Polyphagotarsonemus spp, Psoroptes spp., Rhipicephalusspp., Rhizoglyphus spp., Sarcoptes spp., Steneotarsonemus spp,Tarsonemus spp. and Tetranychus spp.;

from the order Anoplura, for example,

Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp. andPhylloxera spp.; from the order Coleoptera, for example,

Agriotes spp., Amphimallon majale, Anomala orientalis, Anthonomus spp.,Aphodius spp, Astylus atromaculatus, Ataenius spp, Atomaria linearis,Chaetocnema tibialis, Cerotoma spp, Conoderus spp, Cosmopolites spp.,Cotinis nitida, Curculio spp., Cyclocephala spp, Dermestes spp.,Diabrotica spp., Diloboderus abderus, Epilachna spp., Eremnus spp.,Heteronychus arator, Hypothenemus hampei, Lagria vilosa, Leptinotarsadecemlineata, Lissorhoptrus spp., Liogenys spp, Maecolaspis spp,Maladera castanea, Megascelis spp, Melighetes aeneus, Melolontha spp.,Myochrous armatus, Orycaephilus spp., Otiorhynchus spp., Phyllophagaspp, Phlyctinus spp., Popillia spp., Psylliodes spp., Rhyssomatusaubtilis, Rhizopertha spp., Scarabeidae, Sitophilus spp., Sitotrogaspp., Somaticus spp, Sphenophorus spp, Sternechus subsignatus, Tenebriospp., Tribolium spp. and Trogoderma spp.; from the order Diptera, forexample,

Aedes spp., Anopheles spp, Antherigona soccata, Bactrocea oleae, Bibiohortulanus, Bradysia spp, Calliphora erythrocephala, Ceratitis spp.,Chrysomyia spp., Culex spp., Cuterebra spp., Dacus spp., Delia spp,Drosophila melanogaster, Fannia spp., Gastrophilus spp., Geomyzatripunctata, Glossina spp., Hypoderma spp., Hyppobosca spp., Liriomyzaspp., Lucilia spp., Melanagromyza spp., Musca spp., Oestrus spp.,Orseolia spp., Oscinella frit, Pegomyia hyoscyami, Phorbia spp.,Rhagoletis spp, Rivelia quadrifasciata, Scatella spp, Sciara spp.,Stomoxys spp., Tabanus spp., Tannia spp. and Tipula spp.;

from the order Hemiptera, for example,

Acanthocoris scabrator, Acrosternum spp, Adelphocoris lineolatus,Aleurodes spp., Amblypelta nitida, Bathycoelia thalassina, Blissus spp,Cimex spp., Clavigralla tomentosicollis, Creontiades spp, Distantiellatheobroma, Dichelops furcatus, Dysdercus spp., Edessa spp, Euchistusspp., Eurydema pulchrum, Eurygaster spp., Halyomorpha halys, Horciasnobilellus, Leptocorisa spp., Lygus spp, Margarodes spp, Murgantiahistrionic, Neomegalotomus spp, Nesidiocoris tenuis, Nezara spp., Nysiussimulans, Oebalus insularis, Piesma spp., Piezodorus spp, Rhodnius spp.,Sahlbergella singularis, Scaptocoris castanea, Scotinophara spp.,Thyanta spp, Triatoma spp., Vatiga illudens; Acyrthosium pisum, Adalgesspp, Agalliana ensigera, Agonoscena targionii, Aleurodicus spp,Aleurocanthus spp, Aleurolobus barodensis, Aleurothrixus floccosus,Aleyrodes brassicae, Amarasca biguttula, Amritodus atkinsoni, Aonidiellaspp., Aphididae, Aphis spp., Aspidiotus spp., Aulacorthum solani,Bactericera cockerelli, Bemisia spp, Brachycaudus spp, Brevicorynebrassicae, Cacopsylla spp, Cavariella aegopodii Scop., Ceroplaster spp.,Chrysomphalus aonidium, Chrysomphalus dictyospermi, Cicadella spp,Cofana spectra, Cryptomyzus spp, Cicadulina spp, Coccus hesperidum,Dalbulus maidis, Dialeurodes spp, Diaphorina citri, Diuraphis noxia,Dysaphis spp, Empoasca spp., Eriosoma larigerum, Erythroneura spp.,Gascardia spp., Glycaspis brimblecombei, Hyadaphis pseudobrassicae,Hyalopterus spp, Hyperomyzus pallidus, Idioscopus clypealis, Jacobiascalybica, Laodelphax spp., Lecanium corni, Lepidosaphes spp., Lopaphiserysimi, Lyogenys maidis, Macrosiphum spp., Mahanarva spp, Metcalfapruinosa, Metopolophium dirhodum, Myndus crudus, Myzus spp.,Neotoxoptera sp, Nephotettix spp., Nilaparvata spp., Nippolachnus piriMats, Odonaspis ruthae, Oregma lanigera Zehnter, Parabemisia myricae,Paratrioza cockerelli, Parlatoria spp., Pemphigus spp., Peregrinusmaidis, Perkinsiella spp, Phorodon humuli, Phylloxera spp, Planococcusspp., Pseudaulacaspis spp., Pseudococcus spp., Pseudatomoscelisseriatus, Psylla spp., Pulvinaria aethiopica, Quadraspidiotus spp.,Quesada gigas, Recilia dorsalis, Rhopalosiphum spp., Saissetia spp.,Scaphoideus spp., Schizaphis spp., Sitobion spp., Sogatella furcifera,Spissistilus festinus, Tarophagus Proserpina, Toxoptera spp,Trialeurodes spp, Tridiscus sporoboli, Trionymus spp, Trioza erytreae,Unaspis citri, Zygina flammigera, Zyginidia scutellaris;

from the order Hymenoptera, for example,

Acromyrmex, Arge spp, Atta spp., Cephus spp., Diprion spp., Diprionidae,Gilpinia polytoma, Hoplocampa spp., Lasius spp., Monomorium pharaonis,Neodiprion spp., Pogonomyrmex spp, Slenopsis invicta, Solenopsis spp.and Vespa spp.;

from the order Isoptera, for example,

Coptotermes spp, Corniternes cumulans, Incisitermes spp, Macrotermesspp, Mastotermes spp, Microtermes spp, Reticulitermes spp.; Solenopsisgeminate

from the order Lepidoptera, for example,

Acleris spp., Adoxophyes spp., Aegeria spp., Agrotis spp., Alabamaargillaceae, Amylois spp., Anticarsia gemmatalis, Archips spp.,Argyresthia spp, Argyrotaenia spp., Autographa spp., Bucculatrixthurberiella, Busseola fusca, Cadra cautella, Carposina nipponensis,Chilo spp., Choristoneura spp., Chrysoteuchia topiaria, Clysiaambiguella, Cnaphalocrocis spp., Cnephasia spp., Cochylis spp.,Coleophora spp., Colias lesbia, Cosmophila flava, Crambus spp,Crocidolomia binotalis, Cryptophlebia leucotreta, Cydalima perspectalis,Cydia spp., Diaphania perspectalis, Diatraea spp., Diparopsis castanea,Earias spp., Elasmopalpus lignosellus, Eldana saccharina, Ephestia spp.,Epinotia spp, Estigmene acrea, Etiella zinckinella, Eucosma spp.,Eupoecilia ambiguella, Euproctis spp., Euxoa spp., Feltia jaculiferia,Grapholita spp., Hedya nubiferana, Heliothis spp., Hellula undalis,Herpetogramma spp, Hyphantria cunea, Keiferia lycopersicella,Lasmopalpus lignosellus, Leucoptera scitella, Lithocollethis spp.,Lobesia botrana, Loxostege bifidalis, Lymantria spp., Lyonetia spp.,Malacosoma spp., Mamestra brassicae, Manduca sexta, Mythimna spp, Noctuaspp, Operophtera spp., Orniodes indica, Ostrinia nubilalis, Pammenespp., Pandemis spp., Panolis flammea, Papaipema nebris, Pectinophoragossypiela, Perileucoptera coffeella, Pseudaletia unipuncta, Phthorimaeaoperculella, Pieris rapae, Pieris spp., Plutella xylostella, Prays spp.,Pseudoplusia spp, Rachiplusia nu, Richia albicosta, Scirpophaga spp.,Sesamia spp., Sparganothis spp., Spodoptera spp., Sylepta derogate,Synanthedon spp., Thaumetopoea spp., Tortrix spp., Trichoplusia ni, Tutaabsoluta, and Yponomeuta spp.;

from the order Mallophaga, for example,

Damalinea spp. and Trichodectes spp.;

from the order Orthoptera, for example,

Blatta spp., Blattella spp., Gryllotalpa spp., Leucophaea maderae,Locusta spp., Neocurtilla hexadactyla, Periplaneta spp., Scapteriscusspp, and Schistocerca spp.;

from the order Psocoptera, for example,

Liposcelis spp.;

from the order Siphonaptera, for example,

Ceratophyllus spp., Ctenocephalides spp. and Xenopsylla cheopis;

from the order Thysanoptera, for example,

Calliothrips phaseoli, Frankliniella spp., Heliothrips spp,Hercinothrips spp., Parthenothrips spp, Scirtothrips aurantii,Sericothrips variabilis, Taeniothrips spp., Thrips spp;

from the order Thysanura, for example, Lepisma saccharina.

In a further aspect, the invention may also relate to a method ofcontrolling damage to plant and parts thereof by plant parasiticnematodes (Endoparasitic-, Semiendoparasitic- and Ectoparasiticnematodes), especially plant parasitic nematodes such as root knotnematodes, Meloidogyne hapla, Meloidogyne incognita, Meloidogynejavanica, Meloidogyne arenaria and other Meloidogyne species;cyst-forming nematodes, Globodera rostochiensis and other Globoderaspecies; Heterodera avenae, Heterodera glycines, Heterodera schachtii,Heterodera trifolii, and other Heterodera species; Seed gall nematodes,Anguina species; Stem and foliar nematodes, Aphelenchoides species;Sting nematodes, Belonolaimus longicaudatus and other Belonolaimusspecies; Pine nematodes, Bursaphelenchus xylophilus and otherBursaphelenchus species; Ring nematodes, Criconema species, Criconemellaspecies, Criconemoides species, Mesocriconema species; Stem and bulbnematodes, Ditylenchus destructor, Ditylenchus dipsaci and otherDitylenchus species; Awl nematodes, Dolichodorus species; Spiralnematodes, Heliocotylenchus multicinctus and other Helicotylenchusspecies; Sheath and sheathoid nematodes, Hemicycliophora species andHemicriconemoides species; Hirshmanniella species; Lance nematodes,Hoploaimus species; false rootknot nematodes, Nacobbus species; Needlenematodes, Longidorus elongatus and other Longidorus species; Pinnematodes, Pratylenchus species; Lesion nematodes, Pratylenchusneglectus, Pratylenchus penetrans, Pratylenchus curvitatus, Pratylenchusgoodeyi and other Pratylenchus species; Burrowing nematodes, Radopholussimilis and other Radopholus species; Reniform nematodes, Rotylenchusrobustus, Rotylenchus reniformis and other Rotylenchus species;Scutellonema species; Stubby root nematodes, Trichodorus primitivus andother Trichodorus species, Paratrichodorus species; Stunt nematodes,Tylenchorhynchus claytoni, Tylenchorhynchus dubius and otherTylenchorhynchus species; Citrus nematodes, Tylenchulus species; Daggernematodes, Xiphinema species; and other plant parasitic nematodespecies, such as Subanguina spp., Hypsoperine spp., Macroposthonia spp.,Melinius spp., Punctodera spp., and Quinisulcius spp.

The compounds of the invention may also have activity against themolluscs. Examples of which include, for example, Ampullariidae; Arion(A. ater, A. circumscriptus, A. hortensis, A. rufus); Bradybaenidae(Bradybaena fruticum); Cepaea (C. hortensis, C. Nemoralis); ochlodina;Deroceras (D. agrestis, D. empiricorum, D. laeve, D. reticulatum);Discus (D. rotundatus); Euomphalia; Galba (G. trunculata); Helicelia (H.itala, H. obvia); Helicidae Helicigona arbustorum); Helicodiscus; Helix(H. aperta); Limax (L. cinereoniger, L. flavus, L. marginatus, L.maximus, L. tenellus); Lymnaea; Milax (M. gagates, M. marginatus, M.sowerbyi); Opeas; Pomacea (P. canaticulata); Vallonia and Zanitoides.

The active ingredients according to the invention can be used forcontrolling, i. e. containing or destroying, pests of the abovementionedtype which occur in particular on plants, especially on useful plantsand ornamentals in agriculture, in horticulture and in forests, or onorgans, such as fruits, flowers, foliage, stalks, tubers or roots, ofsuch plants, and in some cases even plant organs which are formed at alater point in time remain protected against these pests.

Suitable target crops are, in particular, cereals, such as wheat,barley, rye, oats, rice, maize or sorghum; beet, such as sugar or fodderbeet; fruit, for example pomaceous fruit, stone fruit or soft fruit,such as apples, pears, plums, peaches, almonds, cherries or berries, forexample strawberries, raspberries or blackberries; leguminous crops,such as beans, lentils, peas or soya; oil crops, such as oilseed rape,mustard, poppies, olives, sunflowers, coconut, castor, cocoa or groundnuts; cucurbits, such as pumpkins, cucumbers or melons; fibre plants,such as cotton, flax, hemp orjute; citrus fruit, such as oranges,lemons, grapefruit or tangerines; vegetables, such as spinach, lettuce,asparagus, cabbages, carrots, onions, tomatoes, potatoes or bellpeppers; Lauraceae, such as avocado, Cinnamonium or camphor; and alsotobacco, nuts, coffee, eggplants, sugarcane, tea, pepper, grapevines,hops, the plantain family and latex plants.

The compositions and/or methods of the present invention may be alsoused on any ornamental and/or vegetable crops, including flowers,shrubs, broad-leaved trees and evergreens.

For example the invention may be used on any of the following ornamentalspecies: Ageratum spp., Alonsoa spp., Anemone spp., Anisodonteacapsenisis, Anthemis spp., Antirrhinum spp., Aster spp., Begonia spp.(e.g. B. elatior, B. semperflorens, B. tubereux), Bougainvillea spp.,Brachycome spp., Brassica spp. (ornamental), Calceolaria spp., Capsicumannuum, Catharanthus roseus, Canna spp., Centaurea spp., Chrysanthemumspp., Cineraria spp. (C. maritime), Coreopsis spp., Crassula coccinea,Cuphea ignea, Dahlia spp., Delphinium spp., Dicentra spectabilis,Dorotheantus spp., Eustoma grandiflorum, Forsythia spp., Fuchsia spp.,Geranium gnaphalium, Gerbera spp., Gomphrena globosa, Heliotropium spp.,Helianthus spp., Hibiscus spp., Hortensia spp., Hydrangea spp.,Hypoestes phyllostachya, Impatiens spp. (I. Walleriana), Iresines spp.,Kalanchoe spp., Lantana camara, Lavatera trimestris, Leonotis leonurus,Lilium spp., Mesembryanthemum spp., Mimulus spp., Monarda spp., Nemesiaspp., Tagetes spp., Dianthus spp. (carnation), Canna spp., Oxalis spp.,Bellis spp., Pelargonium spp. (P. peltatum, P. Zonale), Viola spp.(pansy), Petunia spp., Phlox spp., Plecthranthus spp., Poinsettia spp.,Parthenocissus spp. (P. quinquefolia, P. tricuspidata), Primula spp.,Ranunculus spp., Rhododendron spp., Rosa spp. (rose), Rudbeckia spp.,Saintpaulia spp., Salvia spp., Scaevola aemola, Schizanthuswisetonensis, Sedum spp., Solanum spp., Surfinia spp., Tagetes spp.,Nicotinia spp., Verbena spp., Zinnia spp. and other bedding plants.

For example the invention may be used on any of the following vegetablespecies: Allium spp. (A. sativum, A. cepa, A. oschaninii, A. Porrum, A.ascalonicum, A. fistulosum), Anthriscus cerefolium, Apium graveolus,Asparagus officinalis, Beta vulgarus, Brassica spp. (B. Oleracea, B.Pekinensis, B. rapa), Capsicum annuum, Cicer arietinum, Cichoriumendivia, Cichorum spp. (C. intybus, C. endivia), Citrillus lanatus,Cucumis spp. (C. sativus, C. melo), Cucurbita spp. (C. pepo, C. maxima),Cyanara spp. (C. scolymus, C. cardunculus), Daucus carota, Foeniculumvulgare, Hypericum spp., Lactuca sativa, Lycopersicon spp. (L.esculentum, L. lycopersicum), Mentha spp., Ocimum basilicum,Petroselinum crispum, Phaseolus spp. (P. vulgaris, P. coccineus), Pisumsativum, Raphanus sativus, Rheum rhaponticum, Rosemarinus spp., Salviaspp., Scorzonera hispanica, Solanum melongena, Spinacea oleracea,Valerianella spp. (V. locusta, V. eriocarpa) and Vicia faba.

Preferred ornamental species include African violet, Begonia, Dahlia,Gerbera, Hydrangea, Verbena, Rosa, Kalanchoe, Poinsettia, Aster,Centaurea, Coreopsis, Delphinium, Monarda, Phlox, Rudbeckia, Sedum,Petunia, Viola, Impatiens, Geranium, Chrysanthemum, Ranunculus, Fuchsia,Salvia, Hortensia, rosemary, sage, St. Johnswort, mint, sweet pepper,tomato and cucumber.

The active ingredients according to the invention are especiallysuitable for controlling Aphis craccivora, Diabrotica balteata,Heliothis virescens, Myzus persicae, Plutella xylostella and Spodopteralittoralis in cotton, vegetable, maize, rice and soya crops. The activeingredients according to the invention are further especially suitablefor controlling Mamestra (preferably in vegetables), Cydia pomonella(preferably in apples), Empoasca (preferably in vegetables, vineyards),Leptinotarsa (preferably in potatoes) and Chilo supressalis (preferablyin rice).

The compounds of formula I are particularly suitable for control of

-   -   a pest of the order Hemiptera, for example, one or more of the        species Bemisia tabaci, Aphis craccivora, Myzus persicae,        Rhopalosiphum Padi, Nilaparvata lugens, and Euschistus heros        (preferably in vegetables, soybeans, and sugarcane);    -   a pest of the order Lepidoptera, for example, one or more of the        species Spodoptera littoralis, Spodoptera frugiperda, Plutella        xylostella, Cnaphalocrocis medinalis, Cydia pomonella,        Chrysodeixis includes, Chilo suppressalis, Elasmopalpus        lignosellus, Pseudoplusia includens, and Tuta absoluta        (preferably in vegetables and corn);    -   a pest of the order Thysanoptera, such as the family Thripidae,        for example, one or more of Thrips tabaci and Frankliniella        occidentalis (preferably in vegetables); and    -   soil pests (such as of the order Coleoptera), for example, the        species Diabrotica balteata, Agriotes spp. and Leptinotarsa        decemlineata (preferably in vegetables and corn).

The term “crops” is to be understood as including also crop plants whichhave been so transformed by the use of recombinant DNA techniques thatthey are capable of synthesising one or more selectively acting toxins,such as are known, for example, from toxin-producing bacteria,especially those of the genus Bacillus.

Toxins that can be expressed by such transgenic plants include, forexample, insecticidal proteins, for example insecticidal proteins fromBacillus cereus or Bacillus popilliae; or insecticidal proteins fromBacillus thuringiensis, such as □-endotoxins, e.g. Cry1Ab, Cry1Ac,Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetativeinsecticidal proteins (Vip), e.g. Vip1, Vip2, Vip3 or Vip3A; orinsecticidal proteins of bacteria colonising nematodes, for examplePhotorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens,Xenorhabdus nematophilus; toxins produced by animals, such as scorpiontoxins, arachnid toxins, wasp toxins and other insect-specificneurotoxins; toxins produced by fungi, such as Streptomycetes toxins,plant lectins, such as pea lectins, barley lectins or snowdrop lectins;agglutinins; proteinase inhibitors, such as trypsin inhibitors, serineprotease inhibitors, patatin, cystatin, papain inhibitors;ribosome-inactivating proteins (RIP), such as ricin, maize-RIP, abrin,luffin, saporin or bryodin; steroid metabolism enzymes, such as3-hydroxysteroidoxidase, ecdysteroid-UDP-glycosyl-transferase,cholesterol oxidases, ecdysone inhibitors, HMG-COA-reductase, ionchannel blockers, such as blockers of sodium or calcium channels,juvenile hormone esterase, diuretic hormone receptors, stilbenesynthase, bibenzyl synthase, chitinases and glucanases.

In the context of the present invention there are to be understood by□-endotoxins, for example Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A,Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for exampleVip1, Vip2, Vip3 or Vip3A, expressly also hybrid toxins, truncatedtoxins and modified toxins. Hybrid toxins are produced recombinantly bya new combination of different domains of those proteins (see, forexample, WO 02/15701). Truncated toxins, for example a truncated Cry1Ab,are known. In the case of modified toxins, one or more amino acids ofthe naturally occurring toxin are replaced. In such amino acidreplacements, preferably non-naturally present protease recognitionsequences are inserted into the toxin, such as, for example, in the caseof Cry3A055, a cathepsin-G-recognition sequence is inserted into a Cry3Atoxin (see WO 03/018810).

Examples of such toxins or transgenic plants capable of synthesisingsuch toxins are disclosed, for example, in EP-A-0 374 753, WO 93/07278,WO 95/34656, EP-A-0 427 529, EP-A-451 878 and WO 03/052073.

The processes for the preparation of such transgenic plants aregenerally known to the person skilled in the art and are described, forexample, in the publications mentioned above. Cry1-type deoxyribonucleicacids and their preparation are known, for example, from WO 95/34656,EP-A-0 367 474, EP-A-0 401 979 and WO 90/13651.

The toxin contained in the transgenic plants imparts to the plantstolerance to harmful insects. Such insects can occur in any taxonomicgroup of insects, but are especially commonly found in the beetles(Coleoptera), two-winged insects (Diptera) and moths (Lepidoptera).

Transgenic plants containing one or more genes that code for aninsecticidal resistance and express one or more toxins are known andsome of them are commercially available. Examples of such plants are:YieldGard® (maize variety that expresses a Cry1Ab toxin); YieldGardRootworm® (maize variety that expresses a Cry3Bb1 toxin); YieldGardPlus® (maize variety that expresses a Cry1Ab and a Cry3Bb1 toxin);Starlink® (maize variety that expresses a Cry9C toxin); Herculex I®(maize variety that expresses a Cry1 Fa2 toxin and the enzymephosphinothricine N-acetyltransferase (PAT) to achieve tolerance to theherbicide glufosinate ammonium); NuCOTN 33B® (cotton variety thatexpresses a Cry1Ac toxin); Bollgard I® (cotton variety that expresses aCry1Ac toxin); Bollgard II® (cotton variety that expresses a Cry1Ac anda Cry2Ab toxin); VipCot® (cotton variety that expresses a Vip3A and aCry1Ab toxin); NewLeaf® (potato variety that expresses a Cry3A toxin);NatureGard®, Agrisure® GT Advantage (GA21 glyphosate-tolerant trait),Agrisure® CB Advantage (Bt11 corn borer (CB) trait) and Protecta®.

Further examples of such transgenic crops are:

1. Bt11 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790St. Sauveur, France, registration number C/FR/96/05/10. Geneticallymodified Zea mays which has been rendered resistant to attack by theEuropean corn borer (Ostrinia nubilalis and Sesamia nonagrioides) bytransgenic expression of a truncated Cry1Ab toxin. Bt11 maize alsotransgenically expresses the enzyme PAT to achieve tolerance to theherbicide glufosinate ammonium.

2. Bt176 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790St. Sauveur, France, registration number C/FR/96/05/10. Geneticallymodified Zea mays which has been rendered resistant to attack by theEuropean corn borer (Ostrinia nubilalis and Sesamia nonagrioides) bytransgenic expression of a Cry1Ab toxin. Btl76 maize also transgenicallyexpresses the enzyme PAT to achieve tolerance to the herbicideglufosinate ammonium.

3. MIR604 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790St. Sauveur, France, registration number C/FR/96/05/10. Maize which hasbeen rendered insect-resistant by transgenic expression of a modifiedCry3A toxin. This toxin is Cry3A055 modified by insertion of acathepsin-G-protease recognition sequence. The preparation of suchtransgenic maize plants is described in WO 03/018810.

4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren,B-1150 Brussels, Belgium, registration number C/DE/02/9. MON 863expresses a Cry3Bb1 toxin and has resistance to certain Coleopterainsects.

5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de Tervuren,B-1150 Brussels, Belgium, registration number C/ES/96/02.

6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7B-1160 Brussels, Belgium, registration number C/NL/00/10. Geneticallymodified maize for the expression of the protein Cry1F for achievingresistance to certain Lepidoptera insects and of the PAT protein forachieving tolerance to

the herbicide glufosinate ammonium. 7. NK603×MON 810 Maize from MonsantoEurope S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium,registration number C/GB/02/M3/03. Consists of conventionally bredhybrid maize varieties by crossing the genetically modified varietiesNK603 and MON 810. NK603×MON 810 Maize transgenically expresses theprotein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, whichimparts tolerance to the herbicide Roundup® (contains glyphosate), andalso a Cry1Ab toxin obtained from Bacillus thuringiensis subsp. kurstakiwhich brings about tolerance to certain Lepidoptera, include theEuropean corn borer.

Transgenic crops of insect-resistant plants are also described in BATS(Zentrum für Biosicherheit und Nachhaltigkeit, Zentrum BATS,Clarastrasse 13, 4058 Basel, Switzerland) Report 2003, (http://bats.ch).

The term “crops” is to be understood as including also crop plants whichhave been so transformed by the use of recombinant DNA techniques thatthey are capable of synthesising antipathogenic substances having aselective action, such as, for example, the so-called“pathogenesis-related proteins” (PRPs, see e.g. EP-A-0 392 225).Examples of such antipathogenic substances and transgenic plants capableof synthesising such antipathogenic substances are known, for example,from EP-A-0 392 225, WO 95/33818 and EP-A-0 353 191. The methods ofproducing such transgenic plants are generally known to the personskilled in the art and are described, for example, in the publicationsmentioned above.

Crops may also be modified for enhanced resistance to fungal (forexample Fusarium, Anthracnose, or Phytophthora), bacterial (for examplePseudomonas) or viral (for example potato leafroll virus, tomato spottedwilt virus, cucumber mosaic virus) pathogens.

Crops also include those that have enhanced resistance to nematodes,such as the soybean cyst nematode.

Crops that are tolerance to abiotic stress include those that haveenhanced tolerance to drought, high salt, high temperature, chill,frost, or light radiation, for example through expression of NF-YB orother proteins known in the art.

Antipathogenic substances which can be expressed by such transgenicplants include, for example, ion channel blockers, such as blockers forsodium and calcium channels, for example the viral KP1, KP4 or KP6toxins; stilbene synthases; bibenzyl synthases; chitinases; glucanases;the so-called “pathogenesis-related proteins” (PRPs; see e.g. EP-A-0 392225); antipathogenic substances produced by microorganisms, for examplepeptide antibiotics or heterocyclic antibiotics (see e.g. WO 95/33818)or protein or polypeptide factors involved in plant pathogen defence(so-called “plant disease resistance genes”, as described in WO03/000906).

Further areas of use of the compositions according to the invention arethe protection of stored goods and store rooms and the protection of rawmaterials, such as wood, textiles, floor coverings or buildings, andalso in the hygiene sector, especially the protection of humans,domestic animals and productive livestock against pests of the mentionedtype.

The present invention provides a compound of the first aspect for use intherapy. The present invention provides a compound of the first aspect,for use in controlling parasites in or on an animal. The presentinvention further provides a compound of the first aspect, for use incontrolling ectoparasites on an animal. The present invention furtherprovides a compound of the first aspect, for use in preventing and/ortreating diseases transmitted by ectoparasites.

The present invention provides the use of a compound of the firstaspect, for the manufacture of a medicament for controlling parasites inor on an animal. The present invention further provides the use of acompound of the first aspect, for the manufacture of a medicament forcontrolling ectoparasites on an animal. The present invention furtherprovides the use of a compound of the first aspect, for the manufactureof a medicament for preventing and/or treating diseases transmitted byectoparasites.

The present invention provides the use of a compound of the firstaspect, in controlling parasites in or on an animal. The presentinvention further provides the use of a compound of the first aspect, incontrolling ectoparasites on an animal.

The term “controlling” when used in context of parasites in or on ananimal refers to reducing the number of pests or parasites, eliminatingpests or parasites and/or preventing further pest or parasiteinfestation.

The term “treating” when used in context of parasites in or on an animalrefers to restraining, slowing, stopping or reversing the progression orseverity of an existing symptom or disease. The term “preventing” whenused in context of parasites in or on an animal refers to the avoidanceof a symptom or disease developing in the animal.

The term “animal” when used in context of parasites in or on an animalmay refer to a mammal and a non-mammal, such as a bird or fish. In thecase of a mammal, it may be a human or non-human mammal. Non-humanmammals include, but are not limited to, livestock animals and companionanimals. Livestock animals include, but are not limited to, cattle,camelids, pigs, sheep, goats and horses. Companion animals include, butare not limited to, dogs, cats and rabbits.

A “parasite” is a pest which lives in or on the host animal and benefitsby deriving nutrients at the host animal's expense. An “endoparasite” isa parasite which lives in the host animal. An “ectoparasite” is aparasite which lives on the host animal. Ectoparasites include, but arenot limited to, acari, insects and crustaceans (e.g. sea lice). TheAcari (or Acarina) sub-class comprises ticks and mites. Ticks include,but are not limited to, members of the following genera: Rhipicaphalus,for example, Rhipicaphalus (Boophilus) microplus and Rhipicephalussanguineus; Amblyomma; Dermacentor; Haemaphysalis; Hyalomma; Ixodes;Rhipicentor; Margaropus; Argas; Otobius; and Ornithodoros. Mitesinclude, but are not limited to, members of the following genera:Chorioptes, for example Chorioptes bovis; Psoroptes, for examplePsoroptes ovis; Cheyletiella; Dermanyssus; for example Dermanyssusgallinae; Ortnithonyssus; Demodex, for example Demodex canis; Sarcoptes,for example Sarcoptes scabiei; and Psorergates. Insects include, but arenot limited to, members of the orders: Siphonaptera, Diptera,Phthiraptera, Lepidoptera, Coleoptera and Homoptera. Members of theSiphonaptera order include, but are not limited to, Ctenocephalidesfelis and Ctenocephatides canis. Members of the Diptera order include,but are not limited to, Musca spp.; bot fly, for example Gasterophilusintestinalis and Oestrus ovis; biting flies; horse flies, for exampleHaematopota spp. and Tabunus spp.; haematobia, for example Haematobiairritans; Stomoxys; Lucilia; midges; and mosquitoes. Members of thePhthiraptera class include, but are not limited to, blood sucking liceand chewing lice, for example Bovicola Ovis and Bovicola Bovis.

The term “effective amount” when used in context of parasites in or onan animal refers to the amount or dose of the compound of the invention,or a salt thereof, which, upon single or multiple dose administration tothe animal, provides the desired effect in or on the animal. Theeffective amount can be readily determined by the attendingdiagnostician, as one skilled in the art, by the use of known techniquesand by observing results obtained under analogous circumstances. Indetermining the effective amount a number of factors are considered bythe attending diagnostician, including, but not limited to: the speciesof mammal; its size, age, and general health; the parasite to becontrolled and the degree of infestation; the specific disease ordisorder involved; the degree of involvement or the severity of thedisease or disorder; the response of the individual; the particularcompound administered; the mode of administration; the bioavailabilitycharacteristics of the preparation administered; the dose regimenselected; the use of concomitant medication; and other relevantcircumstances.

The compounds of the invention may be administered to the animal by anyroute which has the desired effect including, but not limited totopically, orally, parenterally and subcutaneously. Topicaladministration is preferred. Formulations suitable for topicaladministration include, for example, solutions, emulsions andsuspensions and may take the form of a pour-on, spot-on, spray-on, sprayrace or dip. In the alternative, the compounds of the invention may beadministered by means of an ear tag or collar.

Salt forms of the compounds of the invention include bothpharmaceutically acceptable salts and veterinary acceptable salts, whichcan be different to agrochemically acceptable salts. Pharmaceuticallyand veterinary acceptable salts and common methodology for preparingthem are well known in the art. See, for example, Gould, P. L., “Saltselection for basic drugs”, International Journal of Pharmaceutics, 33:201-217 (1986); Bastin, R. J., et al. “Salt Selection and OptimizationProcedures for Pharmaceutical New Chemical Entities”, Organic ProcessResearch and Development, 4: 427-435 (2000); and Berge, S. M., et al.,“Pharmaceutical Salts”, Journal of Pharmaceutical Sciences, 66: 1-19,(1977). One skilled in the art of synthesis will appreciate that thecompounds of the invention are readily converted to and may be isolatedas a salt, such as a hydrochloride salt, using techniques and conditionswell known to one of ordinary skill in the art. In addition, one skilledin the art of synthesis will appreciate that the compounds of theinvention are readily converted to and may be isolated as thecorresponding free base from the corresponding salt.

The present invention also provides a method for controlling pests (suchas mosquitoes and other disease vectors; see alsohttp://www.who.int/malaria/vector_control/irs/en/). In one embodiment,the method for controlling pests comprises applying the compositions ofthe invention to the target pests, to their locus or to a surface orsubstrate by brushing, rolling, spraying, spreading or dipping. By wayof example, an IRS (indoor residual spraying) application of a surfacesuch as a wall, ceiling or floor surface is contemplated by the methodof the invention. In another embodiment, it is contemplated to applysuch compositions to a substrate such as non-woven or a fabric materialin the form of (or which can be used in the manufacture of) netting,clothing, bedding, curtains and tents.

In one embodiment, the method for controlling such pests comprisesapplying a pesticidally effective amount of the compositions of theinvention to the target pests, to their locus, or to a surface orsubstrate so as to provide effective residual pesticidal activity on thesurface or substrate. Such application may be made by brushing, rolling,spraying, spreading or dipping the pesticidal composition of theinvention. By way of example, an IRS application of a surface such as awall, ceiling or floor surface is contemplated by the method of theinvention so as to provide effective residual pesticidal activity on thesurface. In another embodiment, it is contemplated to apply suchcompositions for residual control of pests on a substrate such as afabric material in the form of (or which can be used in the manufactureof) netting, clothing, bedding, curtains and tents.

Substrates including non-woven, fabrics or netting to be treated may bemade of natural fibres such as cotton, raffia, jute, flax, sisal,hessian, or wool, or synthetic fibres such as polyamide, polyester,polypropylene, polyacrylonitrile or the like. The polyesters areparticularly suitable. The methods of textile treatment are known, e.g.WO 2008/151984, WO 2003/034823, U.S. Pat. No. 5,631,072, WO 2005/64072,WO2006/128870, EP 1724392, WO 2005113886 or WO 2007/090739.

Further areas of use of the compositions according to the invention arethe field of tree injection/trunk treatment for all ornamental trees aswell all sort of fruit and nut trees.

In the field of tree injection/trunk treatment, the compounds accordingto the present invention are especially suitable against wood-boringinsects from the order Lepidoptera as mentioned above and from the orderColeoptera, especially against woodborers listed in the following tablesA and B:

TABLE A Examples of exotic woodborers of economic importance. Host orCrop Family Species Infested Buprestidae Agrilus planipennis AshCerambycidae Anoplura glabripennis Hardwoods Scolytidae Xylosandruscrassiusculus Hardwoods X. mutilatus Hardwoods Tomicus piniperdaConifers

TABLE B Examples of native woodborers of economic importance. FamilySpecies Host or Crop Infested Buprestidae Agrilus anxius Birch Agriluspolitus Willow, Maple Agrilus sayi Bayberry, Sweetfern Agrilusvittaticolllis Apple, Pear, Cranberry, Serviceberry, HawthornChrysobothris femorata Apple, Apricot, Beech, Boxelder, Cherry,Chestnut, Currant, Elm, Hawthorn, Hackberry, Hickory, Horsechestnut,Linden, Maple, Mountain-ash, Oak, Pecan, Pear, Peach, Persimmon, Plum,Poplar, Quince, Redbud, Serviceberry, Sycamore, Walnut, Willow Texaniacampestris Basswood, Beech, Maple, Oak, Sycamore, Willow, Yellow-poplarCerambycidae Goes pulverulentus Beech, Elm, Nuttall, Willow, Black oak,Cherrybark oak, Water oak, Sycamore Goes tigrinus Oak Neoclytusacuminatus Ash, Hickory, Oak, Walnut, Birch, Beech, Maple, Easternhophornbeam, Dogwood, Persimmon, Redbud, Holly, Hackberry, Black locust,Honeylocust, Yellow-poplar, Chestnut, Osage-orange, Sassafras, Lilac,Mountain-mahogany, Pear, Cherry, Plum, Peach, Apple, Elm, Basswood,Sweetgum Neoptychodes trilineatus Fig, Alder, Mulberry, Willow, Netleafhackberry Oberea ocellata Sumac, Apple, Peach, Plum, Pear, Currant,Blackberry Oberea tripunctata Dogwood, Viburnum, Elm, Sourwood,Blueberry, Rhododendron, Azalea, Laurel, Poplar, Willow, MulberryOncideres cingulata Hickory, Pecan, Persimmon, Elm, Sourwood, Basswood,Honeylocust, Dogwood, Eucalyptus, Oak, Hackberry, Maple, Fruit treesSaperda calcarata Poplar Strophiona nitens Chestnut, Oak, Hickory,Walnut, Beech, Maple Scolytidae Corthylus columbianus Maple, Oak,Yellow-poplar, Beech, Boxelder, Sycamore, Birch, Basswood, Chestnut, ElmDendroctonus frontalis Pine Dryocoetes betulae Birch, Sweetgum, Wildcherry, Beech, Pear Monarthrum fasciatum Oak, Maple, Birch, Chestnut,Sweetgum, Blackgum, Poplar, Hickory, Mimosa, Apple, Peach, PinePhloeotribus liminaris Peach, Cherry, Plum, Black cherry, Elm, Mulberry,Mountain-ash Pseudopityophthorus pruinosus Oak, American beech, Blackcherry, Chickasaw plum, Chestnut, Maple, Hickory, Hornbeam, HophornbeamSesiidae Paranthrene simulans Oak, American chestnut Sanninauroceriformis Persimmon Synanthedon exitiosa Peach, Plum, Nectarine,Cherry, Apricot, Almond, Black cherry Synanthedon pictipes Peach, Plum,Cherry, Beach, Black Cherry Synanthedon rubrofascia Tupelo Synanthedonscitula Dogwood, Pecan, Hickory, Oak, Chestnut, Beech, Birch, Blackcherry, Elm, Mountain-ash, Viburnum, Willow, Apple, Loquat, Ninebark,Bayberry Vitacea polistiformis Grape

The present invention may be also used to control any insect pests thatmay be present in turfgrass, including for example beetles,caterpillars, fire ants, ground pearls, millipedes, sow bugs, mites,mole crickets, scales, mealybugs, ticks, spittlebugs, southern chinchbugs and white grubs. The present invention may be used to controlinsect pests at various stages of their life cycle, including eggs,larvae, nymphs and adults.

In particular, the present invention may be used to control insect peststhat feed on the roots of turfgrass including white grubs (such asCyclocephala spp. (e.g. masked chafer, C. lurida), Rhizotrogus spp.(e.g. European chafer, R. majalis), Cotinus spp. (e.g. Green Junebeetle, C. nitida), Popillia spp. (e.g. Japanese beetle, P. japonica),Phyllophaga spp. (e.g. May/June beetle), Ataenius spp. (e.g. Blackturfgrass ataenius, A. spretulus), Maladera spp. (e.g. Asiatic gardenbeetle, M. castanea) and Tomarus spp.), ground pearls (Margarodes spp.),mole crickets (tawny, southern, and short-winged; Scapteriscus spp.,Gryllotalpa africana) and leatherjackets (European crane fly, Tipulaspp.).

The present invention may also be used to control insect pests ofturfgrass that are thatch dwelling, including armyworms (such as fallarmyworm Spodoptera frugiperda, and common armyworm Pseudaletiaunipuncta), cutworms, billbugs (Sphenophorus spp., such as S. venatusverstitus and S. parvulus), and sod webworms (such as Crambus spp. andthe tropical sod webworm, Herpetogramma phaeopteralis).

The present invention may also be used to control insect pests ofturfgrass that live above the ground and feed on the turfgrass leaves,including chinch bugs (such as southern chinch bugs, Blissus insularis),Bermudagrass mite (Eriophyes cynodoniensis), rhodesgrass mealybug(Antonina graminis), two-lined spittlebug (Propsapia bicincta),leafhoppers, cutworms (Noctuidae family), and greenbugs.

The present invention may also be used to control other pests ofturfgrass such as red imported fire ants (Solenopsis invicta) thatcreate ant mounds in turf.

In the hygiene sector, the compositions according to the invention areactive against ectoparasites such as hard ticks, soft ticks, mangemites, harvest mites, flies (biting and licking), parasitic fly larvae,lice, hair lice, bird lice and fleas.

Examples of such parasites are:

Of the order Anoplurida: Haematopinus spp., Linognathus spp., Pediculusspp. and Phtirus spp., Solenopotes spp.

Of the order Mallophagida: Trimenopon spp., Menopon spp., Trinoton spp.,Bovicola spp., Werneckiella spp., Lepikentron spp., Damalina spp.,Trichodectes spp. and Felicola spp.

Of the order Diptera and the suborders Nematocerina and Brachycerina,for example Aedes spp., Anopheles spp., Culex spp., Simulium spp.,Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp.,Chrysops spp., Hybomitra spp., Atylotus spp., Tabanus spp., Haematopotaspp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp.,Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossinaspp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp.,Sarcophaga spp., Oestrus spp., Hypoderma spp., Gasterophilus spp.,Hippobosca spp., Lipoptena spp. and Melophagus spp.

Of the order Siphonapterida, for example Pulex spp., Ctenocephalidesspp., Xenopsylla spp., Ceratophyllus spp.

Of the order Heteropterida, for example Cimex spp., Triatoma spp.,Rhodnius spp., Panstrongylus spp.

Of the order Blattarida, for example Blatta orientalis, Periplanetaamericana, Blattelagermanica and Supella spp.

Of the subclass Acaria (Acarida) and the orders Meta- and Meso-stigmata,for example Argas spp., Ornithodorus spp., Otobius spp., Ixodes spp.,Amblyomma spp., Boophilus spp., Dermacentor spp., Haemophysalis spp.,Hyalomma spp., Rhipicephalus spp., Dermanyssus spp., Raillietia spp.,Pneumonyssus spp., Sternostoma spp. and Varroa spp.

Of the orders Actinedida (Prostigmata) and Acaridida (Astigmata), forexample Acarapis spp., Cheyletiella spp., Ornithocheyletia spp., Myobiaspp., Psorergates spp., Demodex spp., Trombicula spp., Listrophorusspp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypodectes spp.,Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes spp.,Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp. andLaminosioptes spp.

The compositions according to the invention are also suitable forprotecting against insect infestation in the case of materials such aswood, textiles, plastics, adhesives, glues, paints, paper and card,leather, floor coverings and buildings.

The compositions according to the invention can be used, for example,against the following pests: beetles such as Hylotrupes bajulus,Chlorophorus pilosis, Anobium punctatum, Xestobium rufovillosum,Ptilinuspecticornis, Dendrobium pertinex, Ernobius mollis, Priobiumcarpini, Lyctus brunneus, Lyctus africanus, Lyctus planicollis, Lyctuslinearis, Lyctus pubescens, Trogoxylon aequale, Minthesrugicollis,Xyleborus spec., Tryptodendron spec., Apate monachus, Bostrychuscapucins, Heterobostrychus brunneus, Sinoxylon spec. and Dinoderusminutus, and also hymenopterans such as Sirex juvencus, Urocerus gigas,Urocerus gigas taignus and Urocerus augur, and termites such asKalotermes flavicollis, Cryptotermes brevis, Heterotermes indicola,Reticulitermes flavipes, Reticulitermes santonensis, Reticulitermeslucifugus, Mastotermes darwiniensis, Zootermopsis nevadensis andCoptotermes formosanus, and bristletails such as Lepisma saccharina.

The compounds of formulae I, and I′a, or salts thereof, are especiallysuitable for controlling one or more pests selected from the family:Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae,Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae,Meloidogynidae, and Heteroderidae. In a preferred embodiment of eachaspect, a compound TX (where the abbreviation “TX” means “one compoundselected from the compounds defined in Tables D-1 to D-66 and Table P”)controls one or more of pests selected from the family: Noctuidae,Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae,Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae, andHeteroderidae.

The compounds of formulae I, and I′a, or salts thereof, are especiallysuitable for controlling one or more of pests selected from the genus:Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistusspp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp,Rhopalosiphum spp, Pseudoplusia spp and Chilo spp. In a preferredembodiment of each aspect, a compound TX (where the abbreviation “TX”means “one compound selected from the compounds defined in Tables D-1 toD-66 and Table P”) controls one or more of pests selected from thegenus: Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp,Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp,Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp.

The compounds of formulae I, and I′a, or salts thereof, are especiallysuitable for controlling one or more of Spodoptera littoralis, Plutellaxylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros,Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixisincludens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum padi,and Chilo suppressalis.

In a preferred embodiment of each aspect, a compound TX (where theabbreviation “TX” means “one compound selected from the compoundsdefined in Tables D-1 to D-66 and Table P”) controls one or more ofSpodoptera littoralis, Plutella xylostella, Frankliniella occidentalis,Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens,Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabroticabalteata, Rhopalosiphum Padia, and Chilo Suppressalis, such asSpodoptera littoralis+TX, Plutella xylostella+TX; Frankliniellaoccidentalis+TX, Thrips tabaci+TX, Euschistus heros+TX, Cydiapomonella+TX, Nilaparvata lugens+TX, Myzus persicae+TX, Chrysodeixisincludens+TX, Aphis craccivora+TX, Diabrotica balteata+TX, RhopalosiphumPadi+TX, and Chilo suppressalis+TX.

In an embodiment, of each aspect, one compound from Tables D-1 to D-66and Table P is suitable for controlling Spodoptera littoralis, Plutellaxylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros,Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixisincludens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia,and Chilo Suppressalis in cotton, vegetable, maize, cereal, rice andsoya crops.

In an embodiment, one compound from Tables D-1 to D-66 and Table P issuitable for controlling Mamestra (preferably in vegetables), Cydiapomonella (preferably in apples), Empoasca (preferably in vegetables,vineyards), Leptinotarsa (preferably in potatos) and Chilo supressalis(preferably in rice).

Compounds according to the invention may possess any number of benefitsincluding, inter alia, advantageous levels of biological activity forprotecting plants against insects or superior properties for use asagrochemical active ingredients (for example, greater biologicalactivity, an advantageous spectrum of activity, an increased safetyprofile (against non-target organisms above and below ground (such asfish, birds and bees), improved physico-chemical properties, orincreased biodegradability). In particular, it has been surprisinglyfound that certain compounds of formula I may show an advantageoussafety profile with respect to non-target arthropods, in particularpollinators such as honey bees, solitary bees, and bumble bees. Mostparticularly, Apis mellifera.

The compounds according to the invention can be used as pesticidalagents in unmodified form, but they are generally formulated intocompositions in various ways using formulation adjuvants, such ascarriers, solvents and surface-active substances. The formulations canbe in various physical forms, e.g. in the form of dusting powders, gels,wettable powders, water-dispersible granules, water-dispersible tablets,effervescent pellets, emulsifiable concentrates, microemulsifiableconcentrates, oil-in-water emulsions, oil-flowables, aqueousdispersions, oily dispersions, suspo-emulsions, capsule suspensions,emulsifiable granules, soluble liquids, water-soluble concentrates (withwater or a water-miscible organic solvent as carrier), impregnatedpolymer films or in other forms known e.g. from the Manual onDevelopment and Use of FAO and WHO Specifications for Pesticides, UnitedNations, First Edition, Second Revision (2010). Such formulations caneither be used directly or diluted prior to use. The dilutions can bemade, for example, with water, liquid fertilisers, micronutrients,biological organisms, oil or solvents.

The formulations can be prepared e.g. by mixing the active ingredientwith the formulation adjuvants in order to obtain compositions in theform of finely divided solids, granules, solutions, dispersions oremulsions. The active ingredients can also be formulated with otheradjuvants, such as finely divided solids, mineral oils, oils ofvegetable or animal origin, modified oils of vegetable or animal origin,organic solvents, water, surface-active substances or combinationsthereof.

The active ingredients can also be contained in very fine microcapsules.Microcapsules contain the active ingredients in a porous carrier. Thisenables the active ingredients to be released into the environment incontrolled amounts (e.g. slow-release). Microcapsules usually have adiameter of from 0.1 to 500 microns. They contain active ingredients inan amount of about from 25 to 95% by weight of the capsule weight. Theactive ingredients can be in the form of a monolithic solid, in the formof fine particles in solid or liquid dispersion or in the form of asuitable solution. The encapsulating membranes can comprise, forexample, natural or synthetic rubbers, cellulose, styrene/butadienecopolymers, polyacrylonitrile, polyacrylate, polyesters, polyamides,polyureas, polyurethane or chemically modified polymers and starchxanthates or other polymers that are known to the person skilled in theart. Alternatively, very fine microcapsules can be formed in which theactive ingredient is contained in the form of finely divided particlesin a solid matrix of base substance, but the microcapsules are notthemselves encapsulated.

The formulation adjuvants that are suitable for the preparation of thecompositions according to the invention are known per se. As liquidcarriers there may be used: water, toluene, xylene, petroleum ether,vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acidanhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone,butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkylesters of acetic acid, diacetone alcohol, 1,2-dichloropropane,diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycolabietate, diethylene glycol butyl ether, diethylene glycol ethyl ether,diethylene glycol methyl ether, N,N-dimethylformamide, dimethylsulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methylether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone,ethyl acetate, 2-ethylhexanol, ethylene carbonate,1,1,1-trichloroethane, 2-heptanone, alpha-pinene, d-limonene, ethyllactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycolmethyl ether, gamma-butyrolactone, glycerol, glycerol acetate, glyceroldiacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamylacetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene,isopropyl myristate, lactic acid, laurylamine, mesityl oxide,methoxy-propanol, methyl isoamyl ketone, methyl isobutyl ketone, methyllaurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene,n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleicacid, oleylamine, o-xylene, phenol, polyethylene glycol, propionic acid,propyl lactate, propylene carbonate, propylene glycol, propylene glycolmethyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol,xylenesulfonic acid, paraffin, mineral oil, trichloroethylene,perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propyleneglycol methyl ether, diethylene glycol methyl ether, methanol, ethanol,isopropanol, and alcohols of higher molecular weight, such as amylalcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol,propylene glycol, glycerol, N-methyl-2-pyrrolidone and the like.

Suitable solid carriers are, for example, talc, titanium dioxide,pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone,calcium carbonate, bentonite, calcium montmorillonite, cottonseed husks,wheat flour, soybean flour, pumice, wood flour, ground walnut shells,lignin and similar substances.

A large number of surface-active substances can advantageously be usedin both solid and liquid formulations, especially in those formulationswhich can be diluted with a carrier prior to use. Surface-activesubstances may be anionic, cationic, non-ionic or polymeric and they canbe used as emulsifiers, wetting agents or suspending agents or for otherpurposes. Typical surface-active substances include, for example, saltsof alkyl sulfates, such as diethanolammonium lauryl sulfate; salts ofalkylarylsulfonates, such as calcium dodecylbenzenesulfonate;alkylphenol/alkylene oxide addition products, such as nonylphenolethoxylate; alcohol/alkylene oxide addition products, such astridecylalcohol ethoxylate; soaps, such as sodium stearate; salts ofalkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate;dialkyl esters of sulfosuccinate salts, such as sodiumdi(2-ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitololeate; quaternary amines, such as lauryltrimethylammonium chloride,polyethylene glycol esters of fatty acids, such as polyethylene glycolstearate; block copolymers of ethylene oxide and propylene oxide; andsalts of mono- and di-alkylphosphate esters; and also further substancesdescribed e.g. in McCutcheon's Detergents and Emulsifiers Annual, MCPublishing Corp., Ridgewood N.J. (1981).

Further adjuvants that can be used in pesticidal formulations includecrystallisation inhibitors, viscosity modifiers, suspending agents,dyes, anti-oxidants, foaming agents, light absorbers, mixingauxiliaries, antifoams, complexing agents, neutralising or pH-modifyingsubstances and buffers, corrosion inhibitors, fragrances, wettingagents, take-up enhancers, micronutrients, plasticisers, glidants,lubricants, dispersants, thickeners, antifreezes, microbicides, andliquid and solid fertilisers.

The compositions according to the invention can include an additivecomprising an oil of vegetable or animal origin, a mineral oil, alkylesters of such oils or mixtures of such oils and oil derivatives. Theamount of oil additive in the composition according to the invention isgenerally from 0.01 to 10%, based on the mixture to be applied. Forexample, the oil additive can be added to a spray tank in the desiredconcentration after a spray mixture has been prepared. Preferred oiladditives comprise mineral oils or an oil of vegetable origin, forexample rapeseed oil, olive oil or sunflower oil, emulsified vegetableoil, alkyl esters of oils of vegetable origin, for example the methylderivatives, or an oil of animal origin, such as fish oil or beeftallow. Preferred oil additives comprise alkyl esters of C₈-C₂₂ fattyacids, especially the methyl derivatives of C₁₂-C₁₈ fatty acids, forexample the methyl esters of lauric acid, palmitic acid and oleic acid(methyl laurate, methyl palmitate and methyl oleate, respectively).

Many oil derivatives are known from the Compendium of HerbicideAdjuvants, 10^(th) Edition, Southern Illinois University, 2010.

The inventive compositions generally comprise from 0.1 to 99% by weight,especially from 0.1 to 95% by weight, of compounds of the presentinvention and from 1 to 99.9% by weight of a formulation adjuvant whichpreferably includes from 0 to 25% by weight of a surface-activesubstance.

Whereas commercial products may preferably be formulated asconcentrates, the end user will normally employ dilute formulations.

The rates of application vary within wide limits and depend on thenature of the soil, the method of application, the crop plant, the pestto be controlled, the prevailing climatic conditions, and other factorsgoverned by the method of application, the time of application and thetarget crop. As a general guideline compounds may be applied at a rateof from 1 to 2000 l/ha, especially from 10 to 1000 l/ha.

Preferred formulations can have the following compositions (weight %):

Emulsifiable Concentrates:

active ingredient: 1 to 95%, preferably 60 to 90%

surface-active agent: 1 to 30%, preferably 5 to 20%

liquid carrier: 1 to 80%, preferably 1 to 35%

Dusts:

active ingredient: 0.1 to 10%, preferably 0.1 to 5%

solid carrier: 99.9 to 90%, preferably 99.9 to 99%

Suspension Concentrates:

active ingredient: 5 to 75%, preferably 10 to 50%

water: 94 to 24%, preferably 88 to 30%

surface-active agent: 1 to 40%, preferably 2 to 30%

Wettable Powders:

active ingredient: 0.5 to 90%, preferably 1 to 80%

surface-active agent: 0.5 to 20%, preferably 1 to 15%

solid carrier: 5 to 95%, preferably 15 to 90%

Granules:

active ingredient: 0.1 to 30%, preferably 0.1 to 15%

solid carrier: 99.5 to 70%, preferably 97 to 85%

The following Examples further illustrate, but do not limit, theinvention.

Wettable powders a) b) c) active ingredients 25% 50% 75% sodiumlignosulfonate  5%  5% — sodium lauryl sulfate  3% —  5% sodiumdiisobutylnaphthalenesulfonate —  6% 10% phenol polyethylene glycolether —  2% — (7-8 mol of ethylene oxide) highly dispersed silicic acid 5% 10% 10% Kaolin 62% 27% —

The combination is thoroughly mixed with the adjuvants and the mixtureis thoroughly ground in a suitable mill, affording wettable powders thatcan be diluted with water to give suspensions of the desiredconcentration.

Powders for dry seed treatment a) b) c) active ingredients 25% 50% 75%light mineral oil  5%  5%  5% highly dispersed silicic acid  5%  5% —Kaolin 65% 40% — Talcum — 20%

The combination is thoroughly mixed with the adjuvants and the mixtureis thoroughly ground in a suitable mill, affording powders that can beused directly for seed treatment.

Emulsifiable concentrate active ingredients 10% octylphenol polyethyleneglycol ether  3% (4-5 mol of ethylene oxide) calciumdodecylbenzenesulfonate  3% castor oil polyglycol ether  4% (35 mol ofethylene oxide) Cyclohexanone 30% xylene mixture 50%

Emulsions of any require dilution, which can be use in plant protection,can be obtained from this concentrate by dilution with water.

Dusts a) b) c) Active ingredients  5%  6%  4% Talcum 95% — — Kaolin —94% — mineral filler — — 96%

Ready-for-use dusts are obtained by mixing the combination with thecarrier and grinding the mixture in a suitable mill. Such powders canalso be used for dry dressings for seed.

Extruder granules Active ingredients 15% sodium lignosulfonate  2%carboxymethylcellulose  1% Kaolin 82%

The combination is mixed and ground with the adjuvants, and the mixtureis moistened with water. The mixture is extruded and then dried in astream of air.

Coated granules Active ingredients  8% polyethylene glycol (mol. wt.200)  3% Kaolin 89%

The finely ground combination is uniformly applied, in a mixer, to thekaolin moistened with polyethylene glycol. Non-dusty coated granules areobtained in this manner.

Suspension Concentrate

active ingredients 40% propylene glycol 10% nonylphenol polyethyleneglycol ether  6% (15 mol of ethylene oxide) Sodium lignosulfonate 10%carboxymethylcellulose  1% silicone oil (in the form of a 75%  1%emulsion in water) Water 32%

The finely ground combination is intimately mixed with the adjuvants,giving a suspension concentrate from which suspensions of any desireddilution can be obtained by dilution with water. Using such dilutions,living plants as well as plant propagation material can be treated andprotected against infestation by microorganisms, by spraying, pouring orimmersion.

Flowable Concentrate for Seed Treatment

active ingredients   40% propylene glycol   5% copolymer butanol PO/EO  2% Tristyrenephenole with 10-20 moles EO   2%1,2-benzisothiazolin-3-one  0.5% (in the form of a 20% solution inwater) monoazo-pigment calcium salt   5% Silicone oil (in the form of a75%  0.2% emulsion in water) Water 45.3%

The finely ground combination is intimately mixed with the adjuvants,giving a suspension concentrate from which suspensions of any desireddilution can be obtained by dilution with water. Using such dilutions,living plants as well as plant propagation material can be treated andprotected against infestation by microorganisms, by spraying, pouring orimmersion.

Slow Release Capsule Suspension

28 parts of the combination are mixed with 2 parts of an aromaticsolvent and 7 parts of toluenediisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1). Thismixture is emulsified in a mixture of 1.2 parts of polyvinylalcohol,0.05 parts of a defoamer and 51.6 parts of water until the desiredparticle size is achieved. To this emulsion a mixture of 2.8 parts1,6-diaminohexane in 5.3 parts of water is added. The mixture isagitated until the polymerization reaction is completed. The obtainedcapsule suspension is stabilized by adding 0.25 parts of a thickener and3 parts of a dispersing agent. The capsule suspension formulationcontains 28% of the active ingredients. The medium capsule diameter is8-15 microns. The resulting formulation is applied to seeds as anaqueous suspension in an apparatus suitable for that purpose.

Formulation types include an emulsion concentrate (EC), a suspensionconcentrate (SC), a suspo-emulsion (SE), a capsule suspension (CS), awater dispersible granule (WG), an emulsifiable granule (EG), anemulsion, water in oil (EO), an emulsion, oil in water (EW), amicro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable(OF), an oil miscible liquid (OL), a soluble concentrate (SL), anultra-low volume suspension (SU), an ultra-low volume liquid (UL), atechnical concentrate (TK), a dispersible concentrate (DC), a wettablepowder (WP), a soluble granule (SG) or any technically feasibleformulation in combination with agriculturally acceptable adjuvants.

PREPARATORY EXAMPLES

LCMS Methods:

Method 1:

Spectra were recorded on a Mass Spectrometer from Waters (SQD, SQDIISingle quadrupole mass spectrometer) equipped with an electrospraysource (Polarity: positive and negative ions, Capillary: 3.00 kV, Conerange: 30 V, Extractor: 2.00 V, Source Temperature: 150° C., DesolvationTemperature: 350° C., Cone Gas Flow: 50 l/h, Desolvation Gas Flow: 650l/h, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binarypump, heated column compartment, diode-array detector and ELSD detector.Column: Waters UPLC HSS T3, 1.8 μm, 30×2.1 mm, Temp: 60° C., DADWavelength range (nm): 210 to 500, Solvent Gradient: A=water+5%MeOH+0.05% HCOOH, B=Acetonitrile+0.05% HCOOH, gradient: 10-100% B in 1.2min; Flow (ml/min) 0.85.

Method 2:

Spectra were recorded on a Mass Spectrometer from Waters (SQD, SQDIISingle quadrupole mass spectrometer) equipped with an electrospraysource (Polarity: positive and negative ions, Capillary: 3.00 kV, Conerange: 41 V, Extractor: 2.00 V, Source Temperature: 150° C., DesolvationTemperature: 5000° C., Cone Gas Flow: 50 l/h, Desolvation Gas Flow: 1000l/h, Mass range: 110 to 800 Da) and an Acquity UPLC from Waters: Binarypump, heated column compartment, diode-array detector and ELSD detector.Column: Waters UPLC HSS T3, 1.8 μm, 30×2.1 mm, Temp: 40° C., PDAWavelength range (nm): 200 to 400, Solvent Gradient: A=water+5%Acetonitrile+0.1% HCOOH, B=Acetonitrile+0.05% HCOOH, gradient: 10-100% Bin 1.3 min; Flow (ml/min) 0.6.

Method 3:

Spectra were recorded on a Mass Spectrometer from Waters Corporation(SQD, SQDII or QDA Single quadrupole mass spectrometer) equipped with anelectrospray source (Polarity: positive and negative ions, Capillary:0.8-3.00 kV, Cone: 5-30 V, Source Temperature: 120-150° C., DesolvationTemperature: 350-600° C., Cone Gas Flow: 50-150 l/h, Desolvation GasFlow: 650-1000 l/h, Mass range: 50 to 900 Da and an Acquity UPLC fromWaters Corporation: Binary pump, heated column compartment, diode-arraydetector and ELSD. Column: Waters UPLC HSS T3, 1.8 μm, 30×2.1 mm, Temp:60° C., DAD Wavelength range (nm): 210 to 400, Runtime: 1.5 min;Solvents: A=water+5% MeOH+0.05% HCOOH, B=Acetonitrile+0.05% HCOOH; Flow(ml/min) 0.85, Gradient: 10% B isocratic for 0.2 min, then 10-100% B in1.0 min, 100% B isocratic for 0.2 min, 100-10% B in 0.05 min, 10% Bisocratic for 0.05 min.

Method 4:

Spectra were recorded on a Mass Spectrometer from Waters Corporation(SQD, SQDII or QDA Single quadrupole mass spectrometer) equipped with anelectrospray source (Polarity: positive and negative ions, Capillary:3.00 kV, Cone: 41 V, Source Temperature: 150° C., DesolvationTemperature: 500° C., Cone Gas Flow: 50 l/h, Desolvation Gas Flow: 1000l/h, Mass range: 110 to 800 Da and an Acquity UPLC from WatersCorporation: Binary pump, heated column compartment, diode-arraydetector and ELSD. Column: Waters UPLC HSS T3, 1.8 μm, 30×2.1 mm, Temp:40° C., DAD Wavelength range (nm): 200 to 400, Runtime: 1.6 min;Solvents: A=water+5% Acetonitrile+0.1% HCOOH, B=Acetonitrile+0.05%HCOOH; Flow (ml/min) 0.6, Gradient: 10-50% B in 0.2 min, then 50-100% Bin 0.5 min, 100% B isocratic for 0.6 min, 100-10% B in 0.05 min, 100% to10% B in 0.1 min, then 10% B isocratic for 0.2 min.

Method 5:

Spectra were recorded on a Mass Spectrometer from Agilent Technologies(SQD, SQDII or QDA Single quadrupole mass spectrometer) equipped with anelectrospray source (Polarity: positive and negative ions, Capillary:4.00 kV, Fragmentor: 100 V, Gas Temperature (C): 350, Gas Flow: 11l/min, Mass range: 110 to 1000 Da and an Agilent HPLC from AgilentTechnologies: Column: KINETEX EVO C18, 2.6 μm, 50×4.6 mm, Temp: 40° C.,DAD Wavelength range (nm): 210 to 400, Runtime: 2.5 min; Solvents:A=water+5% Acetonitrile+0.1% HCOOH, B=Acetonitrile+0.1% HCOOH; Flow(ml/min) 1.8, Gradient: 10-100% B in 0.9 min, 100% B isocratic for 0.9min, 100-10% B in 0.4 min, 10% B isocratic for 0.3 min.

Example 1: Preparation ofN-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinolin-4-amine(compound P.5)

Step A: Preparation of5-[[2,4-bis(trifluoromethyl)anilino]methylene]-2,2-dimethyl-1,3-dioxane-4,6-dione(intermediate I-1)

2,2-dimethyl-1,3-dioxane-4,6-dione (3.46 g, 24 mmol, 1.2 equiv.) andtrimethoxymethane (11 mL, 96 mmol, 4.8 equiv.) are heated to reflux for90 mins. Next, 2,4-bis(trifluoromethyl)aniline (4.72 g, 20 mmol, 1equiv.) was added at the same temperature and the solution stirred for50 minutes. Stirring and heating were turned off and a solid startedprecipitating. The solid was collected at room temperature and washedwith cyclohexane and air dried. A second crop of solid can be collectedfrom the filtrate and washed with cyclohexane. The product 1-1 isobtained as an off-white solid (6.27 g, 82%).

¹H NMR (400 MHz, CDCl₃) δ ppm: 1.80 (s, 6H), 7.64 (d, J=8.80 Hz, 1H),7.96 (d, J=8.44 Hz, 1H), 7.98-8.03 (m, 1H), 8.67 (d, J=13.20 Hz, 1H),11.87 (br d, J=12.84 Hz, 1H).

Step B: Preparation of 6,8-bis(trifluoromethyl)-1H-quinolin-4-one(intermediate I-2)

5-[[2,4-bis(trifluoromethyl)anilino]methylene]-2,2-dimethyl-1,3-dioxane-4,6-dione(I-1, 3.12 g, 8.14 mmol) is added to diphenyl ether (15 mL) whilerefluxing. The mixture was stirred at reflux for 30 minutes, thenallowed to cool to room temperature. Reaction was diluted withcyclohexane (20 mL), then the precipitate was filtered and washed withcopious amounts of cyclohexane. The desired product was obtained as alight-brown powder (1.63 g, 71%).

¹H NMR (400 MHz, DMSO-d6) δ ppm: 6.33 (br s, 1H), 7.97 (br s, 1H), 8.33(s, 1H), 8.66 (br s, 1H), 11.57 (br s, 1H).

LC-MS (method 3): retention time 0.86 min, m/z 282 [M+H⁺].

Step C: Preparation of 4-chloro-6,8-bis(trifluoromethyl)quinoline(intermediate I-3)

To a flask containing 6,8-bis(trifluoromethyl)-1H-quinolin-4-one (I-3,2.76 g, 9.81 mmol) was added phosphoryl trichloride (3 mL, 31.5 mmol,3.21 equiv.) and the mixture was stirred at 100° C. for 15 minutes, thenallowed to cool to room temperature, then placed in an ice bath. Thereaction was quenched with water and aqueous ammonia is added till thepH reached 8-9. The mixture was then extracted three times withdichloromethane (3×100 mL) and concentrated under reduced pressure toprovide desired product as a light brown powder (2.5 g, 8.3 mmol, 85%).

¹H NMR (400 MHz, CDCl₃) δ ppm: 7.75 (d, J=4.77 Hz, 1H), 8.34 (s, 1H),8.82 (s, 1H), 9.08 (d, J=4.77 Hz, 1H).

LC-MS (method 3): retention time 1.18 min, m/z 300 [M+H⁺].

Step D: Preparation of(2S)-2-[[6,8-bis(trifluoromethyl)-4-quinolyl]amino]propanamide(intermediate I-4)

To a solution of 4-chloro-6,8-bis(trifluoromethyl)quinoline (I-3, 1.51g, 5.04 mmol) in N,N-dimethylformamide (50 mL) was added(2S)-2-aminopropanamide hydrochloride (3.24 g, 25.2 mmol, 5.00 equiv.)and potassium carbonate (4.88 g, 35.3 mmol, 7 equiv.). The reactionmixture was heated to 100° C. overnight. The reaction was cooled,diluted with water and extracted three times with ethyl acetate. Thecombined organic layers were washed with brine, dried over sodiumsulfate, filtered and concentrated under reduced pressure. Purificationof the crude material by flash chromatography over silica gel (ethylacetate in cyclohexane) afforded the desired product as a brown solid(541 mg, 31% yield).

¹H NMR (400 MHz, DMSO-d6) δ ppm: 1.49-1.58 (m, 3H), 4.09-4.19 (m, 1H),6.49-6.55 (m, 1H), 7.13-7.22 (m, 1H), 7.63-7.71 (m, 1H), 7.83-7.90 (m,1H), 8.17-8.24 (m, 1H), 8.60-8.66 (m, 1H), 9.23-9.29 (m, 1H).

LC-MS (method 3): retention time 0.75 min, m/z 352 [M+H⁺].

Step E: Preparation of(2S)-2-[[6,8-bis(trifluoromethyl)-4-quinolyl]amino]-N-(dimethylaminomethylene)propanamide(compound I-5)

To a solution of(2S)-2-[[6,8-bis(trifluoromethyl)-4-quinolyl]amino]propanamide (I-4,0.74 g, 2.1 mmol) in 2-methyltetrahydrofuran (21 mL) was added1,1-dimethoxy-N,N-dimethyl-methanamine (0.56 mL, 4.2 mmol, 2 equiv.) andthe reaction mixture was stirred at 50° C. for 30 minutes. The reactionwas cooled and concentrated under reduced pressure to provide(2S)-2-[[6,8-bis(trifluoromethyl)-4-quinolyl]amino]-N-(dimethylaminomethylene)propanamide(I-5) as a brown solid (755 mg, 80%).

¹H NMR (400 MHz, DMSO-d6) δ ppm: 1.57 (d, J=6.97 Hz, 3H), 2.98-3.09 (m,3H), 3.10-3.19 (m, 3H), 4.22-4.37 (m, 1H), 6.45-6.55 (m, 1H), 7.83-7.94(m, 1H), 8.17-8.25 (m, 1H), 8.43-8.52 (m, 1H), 8.52-8.60 (m, 1H),9.20-9.31 (m, 1H).

Step F: Preparation ofN-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinolin-4-amine(compound P.5)

(2S)-2-[[6,8-bis(trifluoromethyl)-4-quinolyl]amino]-N-(dimethylaminomethylene)propenamide(I-5 prepared above, 755 mg, 1.86 mmol, 1 equiv.) was dissolved in2-methyltetrahydrofuran (7.4 mL). Next, pyrimidin-2-ylhydrazinehydrochloride (0.49 g, 3.35 mmol) and acetic acid (4.65 mL) were addedand the reaction was stirred at 80° C. for 1 hour. The reaction wascooled, diluted with ethyl acetate and extracted with water. The organiclayer was washed with brine, dried over sodium sulfate, filtered andconcentrated under reduced pressure. Purification of the crude materialby flash chromatography over silica gel (ethyl acetate in cyclohexane)afforded the desired product (P.5) as a light brown solid (631.5 mg, 75%yield).

¹H NMR (400 MHz, DMSO-d6) δ ppm: 1.76 (d, J=6.97 Hz, 3H), 5.96 (quin,J=7.06 Hz, 1H), 6.60 (d, J=5.87 Hz, 1H), 7.51-7.62 (m, 1H), 8.15-8.22(m, 2H), 8.26 (d, J=7.34 Hz, 1H), 8.55 (d, J=5.50 Hz, 1H), 8.92 (d,J=5.14 Hz, 2H), 9.14 (s, 1H).

LC-MS (method 3): retention time 0.88 min, m/z 455 [M+H⁺].

Example 2: Preparation ofN-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinazolin-4-amine(compound P.16)

Step A: Preparation of 2-iodo-4,6-bis(trifluoromethyl)aniline(intermediate I-6)

2,4-Bis(trifluoromethyl)aniline (CAS No. 367-71-5, 1.50 g, 6.2 mmol) wasdissolved in 1,1,1,3,3,3-hexafluoro-2-propanol and the solution cooledto 0° C. N-iodosuccinimide (1.47 g, 6.2 mmol, 1 equiv.) was added andthe reaction stirred at 0° C. for 1 h and then at room temperatureovernight. The reaction was concentrated under reduced pressure and thecrude material purified by flash chromatography over silica gel (ethylacetate in cyclohexane) to obtain product (I-6) as a light pinkcrystalline solid (2.09 g, 95%).

¹H NMR (400 MHz, CDCl₃) δ ppm: 5.08 (br s, 2H), 7.70-7.74 (m, 1H), 8.06(d, J=1.47 Hz, 1H).

Step B: Preparation of 2-amino-3,5-bis(trifluoromethyl)benzonitrile(intermediate I-7)

A sealed tube was charged with 2-iodo-4,6-bis(trifluoromethyl)aniline(I-6, 1.00 g, 2.82 mmol), N,N-dimethylformamide (5.63 mL) and copper(I)cyanide (0.31 g, 3.38 mmol, 1.2 equiv.). The mixture was stirred at 100°C. overnight. The mixture was cooled, filtered through celite andextracted twice with MTBE (2×20 mL). The combined organic layers werewashed with brine, dried over sodium sulfate and concentrated undervacuum. Purification by flash chromatography over silica gel (ethylacetate in cyclohexane) afforded the desired product (I-7) as a brownsolid (567 mg, 79%).

¹H NMR (400 MHz, CDCl₃) δ ppm: 5.33 (br s, 2H), 7.83-7.90 (m, 2H).

¹⁹F NMR (377 MHz, CDCl₃) δ ppm: −63.94 (s, 1 F), −62.19 (s, 1 F).

LC-MS (method 3): retention time 1.01 min, m/z 253 [M−H⁻].

Step C: Preparation of 6,8-bis(trifluoromethyl)quinazolin-4-ol(intermediate I-8)

A flask was charged with 2-amino-3,5-bis(trifluoromethyl)benzonitrile(I-7, 8.8 g, 35 mmol), formic acid (83 mL) and sulfuric acid (2.8 mL, 52mmol, 1.5 equiv.) and the mixture was stirred at 50° C. for 3 hours. Thereaction was then cooled to room temperature and poured slowly in 300 mLof ice-water and stirred for 15 minutes. Resulting solid was filteredoff and dried, resulting in desired product (I-8) as an off-white solid(8.9 g, 91%).

¹H NMR (400 MHz, DMSO-d6) δ ppm: ¹H NMR (400 MHz, Solvent) δ ppm8.31-8.47 (m, 2H), 8.61 (s, 1H), 12.97 (br s, 1H).

LC-MS (method 3): retention time 0.90 min, m/z 283 [M+H⁺].

Step D: Preparation of 4-chloro-6,8-bis(trifluoromethyl)quinazoline(intermediate I-9)

To a solution of 6,8-bis(trifluoromethyl)quinazolin-4-ol (I-8, 0.5 g,5.04 mmol) in thionyl chloride (8.87 mL) was added 5 drops ofN,N-dimethylformamide. The reaction mixture was heated to 100° C. for 1hour, at which point the reaction became homogeneous. The reaction wascooled and concentrated under reduced pressure to afford the desiredproduct (I-9) which was used as such for the next step.

¹H NMR (400 MHz, CDCl₃) δ ppm: 8.50 (s, 1H), 8.84 (s, 1H), 9.33 (s, 1H).

¹⁹F NMR (377 MHz, CDCl₃) δ ppm: −62.86 (s, 1 F), −60.78 (s, 1 F).

LC-MS (method 3): retention time 0.75 min, m/z 352 [M+H⁺].

Step E: Preparation ofN-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinazolin-4-amine(compound P.16)

A flask was charged with 4-chloro-6,8-bis(trifluoromethyl)quinazoline(I-9, 200 mg, 0.67 mmol),1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethylammonium chloride (preparedas in WO2019/197468) (201 mg, 0.80 mmol, 1.2 equiv), potassium carbonate(276 mg, 2.0 mmol, 3 equiv.) and acetonitrile (3 mL) and heated at 80°C. for 4 hours. The reaction was cooled, salts were removed byfiltration and the resulting crude was concentrated under reducedpressure. Purification by flash chromatography over silica gel (ethylacetate in cyclohexane) provided the desired product (P.16) as a beigesolid (120 mg, 40%).

¹H NMR (400 MHz, CDCl₃) δ ppm: 1.85 (d, J=6.97 Hz, 3H), 6.71 (quin,J=6.97 Hz, 1H), 7.49 (t, J=4.77 Hz, 1H), 8.14 (s, 1H), 8.16 (s, 1H),8.27 (br d, J=4.03 Hz, 1H), 8.38 (s, 1H), 8.68 (s, 1H), 9.01 (d, J=4.77Hz, 2H).

LC-MS (method 3): retention time 0.97 min, m/z 455 [M+H⁺].

Example 3: Preparation of2-chloro-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinazolin-4-amine(compound P.25)

Step A: Preparation of 6,8-bis(trifluoromethyl)quinazoline-2,4-diol(intermediate I-10)

A flask was charged with 2-amino-3,5-bis(trifluoromethyl)benzonitrile(I-7 prepared in Example 2, 2 g, 7.87 mmol) and dichloromethane (20 mL).To this mixture was added chlorosulfonyl isocyanate (0.85 mL, 9.44 mmol,1.2 equiv.) and the resulting mixture was stirred for 3 hours. Thereaction was concentrated under reduced pressure and the residue heatedin water (50 mL) at 100° C. for 18 hours. The resulting white solid wasisolated by filtration to provide the desired product (I-10) (800 mg,34%).

¹H NMR (400 MHz, CD₃CN) δ ppm: 8.20-8.23 (m, 1H), 8.50 (s, 1H), 8.73 (brs, 1H), 9.51 (br s, 1H).

Step B: Preparation of 2,4-dichloro-6,8-bis(trifluoromethyl)quinazoline(intermediate I-11)

A flask was charged with 6,8-bis(trifluoromethyl)quinazoline-2,4-diol(I-10, 100 mg, 0.34 mmol) and phosphorous oxychloride (0.32 mL, 3.4mmol, 10 equiv.). To this mixture was then addedN,N-diisopropylethylamine (0.118 mL, 0.67 mmol, 2 equiv.) and theresulting mixture was heated at 100° C. for 2 hours. The reaction wasconcentrated under reduced pressure and the crude material was purifiedby flash chromatography over silica gel (ethyl acetate in cyclohexane)to provide the desired product (I-11) as an off-white solid (84 mg,75%).

¹H NMR (400 MHz, CD3CN) δ ppm: 8.66 (s, 1H), 8.90 (s, 1H).

Step C: Preparation of2-chloro-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinazolin-4-amine(compound P.25)

A flask was charged with2,4-dichloro-6,8-bis(trifluoromethyl)quinazoline (I-11, 100 mg, 0.30mmol), 1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethylammonium chloride(prepared as in WO2019/197468) (68 mg, 0.27 mmol, 0.9 equiv), potassiumcarbonate (123 mg, 0.90 mmol, 3 equiv.) and acetonitrile (1.5 mL) andheated at 80° C. for 16 hours. The reaction was cooled, diluted withwater and extracted two times with ethyl acetate. The combined organiclayers were washed with brine, dried over sodium sulfate, filtered andconcentrated under reduced pressure. Purification of the crude materialby flash chromatography over silica gel (ethyl acetate in cyclohexane)afforded the desired product (P.25) as a pale yellow solid (60 mg, 41%yield).

¹H NMR (400 MHz, DMSO-d6) δ ppm: 1.79 (d, J=6.72 Hz, 3H) 6.38 (t, J=6.72Hz, 1H) 7.65 (t, J=4.65 Hz, 1H) 8.18 (s, 1H) 8.37 (br s, 1H) 8.99 (d,J=4.65 Hz, 2H) 9.24 (br s, 1H) 9.90 (br d, J=6.36 Hz, 1H).

LC-MS (method 4): retention time 1.09 min, m/z 489 [M+H⁺].

Example 4: Preparation ofN-methyl-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinazolin-4-amine(compound P.27)

A flask was charged withN-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinazolin-4-amine(P.16 prepared in Example 2, 148 mg, 0.33 mmol), cesium carbonate (319mg, 0.98 mmol, 3 equiv.), acetonitrile (1.3 mL) and iodomethane (0.041mL, 0.65 mmol, 2 equiv.). The mixture was heated at 50° C. overnight.The reaction was cooled and diluted with water (10 mL). The mixture wasextracted three times with ethyl acetate (3×10 mL) and the combinedorganic layers were washed with brine, dried over sodium sulfate andconcentrated under reduced pressure. Purification by flashchromatography over silica gel (ethyl acetate in cyclohexane) providedthe desired product (P.27) (92 mg, 60%).

¹H NMR (400 MHz, CDCl₃) δ ppm: 1.98 (d, J=6.97 Hz, 3H), 3.37 (s, 3H),6.89 (q, J=6.97 Hz, 1H), 7.23 (t, J=4.95 Hz, 1H), 8.11 (s, 1H), 8.24 (d,J=6.60 Hz, 2H), 8.57 (d, J=4.77 Hz, 2H), 8.60 (s, 1H).

LC-MS (method 3): retention time 0.97 min, m/z 455 [M+H⁺].

¹⁹F NMR (376 MHz, CDCl₃) δ ppm: −62.40 (s, 1 F), −61.33 (s, 1 F).

LC-MS (method 3): retention time 1.01 min, m/z 469 [M+H⁺].

Example 5:8-chloro-N-(cyclopropylmethyl)-2-methoxy-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6-(trifluoromethyl)quinazolin-4-amine(compound P.36)

Step A: Preparation of8-chloro-4-[cyclopropylmethyl-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]amino]-6-(trifluoromethyl)-1H-quinazolin-2-one(intermediate I-12)

A flask was charged with2,8-dichloro-N-(cyclopropylmethyl)-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6-(trifluoromethyl)quinazolin-4-amine(P.49 prepared analogously to P.25 in Example 3, 180 mg, 0.35 mmol) andacetic acid (1.8 mL). This mixture was stirred for 2 hours at 80° C. Thereaction was concentrated under reduced pressure and the residuepurified by reverse-phase chromatography (acetonitrile in water) toprovide the desired product (I-12) (90 mg, 52%).

¹H NMR (400 MHz, DMSO-d6) δ ppm: 0.02-0.07 (m, 1H), 0.09-0.16 (m, 1H),0.25-0.32 (m, 1H), 0.35-0.41 (m, 1H), 0.77-0.85 (m, 1H), 1.87 (d, 3H),3.06 (dd, 1H), 3.36 (dd, 1H), 6.40-6.46 (m, 1H), 7.38 (t, 1H), 7.69 (s,1H), 8.19 (s, 1H), 8.25 (s, 1H), 8.54 (d, 2H), 10.84-10.92 (m, 1H).

Step B: Preparation of8-chloro-N-(cyclopropylmethyl)-2-methoxy-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6-(trifluoromethyl)quinazolin-4-amine(compound P.36)

8-Chloro-4-[cyclopropylmethyl-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]amino]-6-(trifluoromethyl)-1H-quinazolin-2-one(I-12, 35 mg, 0.07 mmol) was dissolved in acetonitrile (0.53 mL) andpotassium carbonate (30 mg, 0.21 mmol, 3 equiv.), followed by dimethylsulfate (7.5 μL, 0.08 mmol, 1.1 equiv) were added. The resulting mixturewas heated at 80° C. for 5 hours. The reaction was cooled and filteredthrough celite with acetonitrile washes. The filtrate was concentratedunder reduced pressure and the crude material was purified byreverse-phase chromatography (acetonitrile in water) to provide thedesired product (P.36) (90 mg, 52%).

¹H NMR (400 MHz, methanol-d4) δ ppm: 0.23 (qd, 1H), 0.31-0.06 (m, 1H),0.55-0.39 (m, 2H), 0.94-0.83 (m, 1H), 2.02 (d, 3H), 3.36 (dd, 1H), 3.56(dd, 1H), 3.97 (s, 3H), 6.78 (q, 1H), 7.29 (t, 1H), 8.08 (d, 1H), 8.18(s, 1H), 8.21 (d, 1H), 8.42 (d, 2H).

LC-MS (method 4): retention time 1.17 min, m/z 505 [M+H⁺].

Example 6: Preparation of6,8-dibromo-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]quinazolin-4-amine(compound P.38)

Step A: Preparation ofN′-(2,4-dibromo-6-cyano-phenyl)-N,N-dimethyl-formamidine (intermediateI-13)

To a solution of 2-amino-3,5-dibromobenzonitrile (CAS No. 68385-95-5,150 mg, 0.54 mmol) in methanol (5 mL) was added1,1-dimethoxy-N,N-dimethyl-methanamine (0.228 mL, 1.63 mmol, 3 equiv.)and the reaction was stirred at 80° C. for 1 hour. The mixture wasconcentrated under reduced pressure to obtain product (I-13) as a solid(179 mg, 99.5%) which was used directly in the next step.

LC-MS (method 3): retention time 1.17 min, m/z 505 [M+H⁺].

Step B: Preparation of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanone(intermediate I-14)

A flask was charged with tributyl(pyrimidin-2-yl)stannane (CAS No.153435-63-3, 25 g, 67.7 mmol, 1 equiv.),1-(3-chloropyrazin-2-yl)ethanone (CAS No. 2142-68-9, 12.37 g, 71.12mmol, 1.05 equiv.) and toluene (500 mL). Reaction mixture was purgedwith nitrogen for 10 minutes and then copper(I) iodide (2.58 g, 13.55mmol, 0.2 equiv.) and tetrakis(triphenylphosphine)palladium(0) (3.91 g,3.39 mmol, 0.05 equiv.) were added. The reaction was then heated at 95°C. for 5 hours. The mixture was cooled, filtered through a pad of celitewith ethyl acetate washings and the filtrate was concentrated underreduced pressure. Purification by flash chromatography over silica gel(ethyl acetate in cyclohexane) afforded product (I-14) as a brown solid(10 g, 51.6%).

LC-MS (method 4): retention time 0.37 min, m/z 201 [M+H⁺].

Step C: Preparation of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanamine(intermediate I-15)

A flask was charged with 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanone (I-14,500 mg, 2.5 mmol, 1 equiv.), ammonium acetate (3.85 g, 50.0 mmol, 20equiv.) and ethanol (25 mL). Next aq. NH₃ (28%) (7.5 mL) and sodiumcyanoborohydride (0.50 g, 7.5 mmol, 3 equiv.) were added and the mixturewas heated at 80° C. for 2 hours. The mixture was cooled andconcentrated under reduced pressure. Purification of the crude materialby reverse-phase column chromatography (C18 40-60 μm, acetonitrile inwater) afforded product (I-15) as a brown gum (210 mg, 42%).

¹H NMR (400 MHz, DMSO-d6) δ ppm: 1.50 (d, J=6.6 Hz, 3H), 4.93 (d, J=6.6Hz, 1H), 7.70 (t, J=5.0 Hz, 1H), 8.86 (d, J=2.3 Hz, 1H), 8.90 (d, J=2.4Hz, 1H), 9.07 (d, J=4.9 Hz, 2H).

Step D: Preparation of6,8-dibromo-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]quinazolin-4-amine(compound P.38)

A vial was charged with 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanone (I-15,120 mg, 0.59 mmol, 1.1 equiv.),N′-(2,4-dibromo-6-cyano-phenyl)-N,N-dimethyl-formamidine (I-13, 179 mg,0.54 mmol, 1 equiv.) and acetic acid (2.7 mL). The mixture was stirredat 120° C. for 1 hour. Another batch of1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanone (I-15, 135 mg) was added andthe stirring continued till reaction completion. The mixture was cooled,diluted with water and extracted with ethyl acetate. The organic layerwas washed with saturated sodium bicarbonate aqueous solution, driedover sodium sulfate and concentrated under reduced pressure.Purification by flash chromatography over silica gel (ethyl acetate incyclohexane), followed by reverse-phase purification (acetonitrile inwater) afforded the desired product (I-7) as a brown solid (83 mg, 32%).

¹H NMR (400 MHz, DMSO-d6) δ ppm: 1.71 (d, J=6.97 Hz, 3H), 5.92 (quin,J=6.79 Hz, 1H), 7.53 (t, J=4.77 Hz, 1H), 8.15 (s, 1H), 8.28 (d, J=1.83Hz, 1H), 8.65 (d, J=1.83 Hz, 1H), 8.66 (d, J=2.57 Hz, 1H), 8.74 (d,J=2.20 Hz, 1H), 8.77 (d, J=6.97 Hz, 1H), 8.92 (d, J=5.14 Hz, 2H).

LC-MS (method 3): retention time 0.87 min, m/z 488 [M+H⁺].

Example 7: Preparation of6-[5-[1-[[2-methyl-6,8-bis(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile(compound P.60)

Step A: Preparation of2-methyl-6,8-bis(trifluoromethyl)quinazolin-4-amine (intermediate I-16)

A sealed tube was charged with2-amino-3,5-bis(trifluoromethyl)benzonitrile (I-7 prepared in Example 2,300 mg, 1.18 mmol) and acetamide (0.7 g, 11.8 mmol, 10 equiv.). Themixture was stirred at 180° C. for 4 days. The reaction was then cooledto room temperature and diluted with water (25 mL). The mixture wasextracted three times with ethyl acetate (3×20 mL) and the combinedorganic layers were washed with brine, dried over sodium sulfate andconcentrated under reduced pressure. The crude material was purified byflash chromatography over silica gel (ethyl acetate in cyclohexane) toprovide desired product (I-16) as a pale yellow solid (102 mg, 29%).

¹⁹F NMR (377 MHz, DMSO-d6) δ ppm: −60.36 (s, 1 F), −59.63 (s, 1 F).

LC-MS (method 3): retention time 0.95 min, m/z 296 [M+H⁺].

Step B: Preparation of6-[5-(1-bromoethyl)-1,2,4-triazol-1-yl]pyridine-3-carbonitrile(intermediate I-18)

To a solution of 2-Bromopropanamide (CAS No. 5875-25-2, 4.00 g, 26.3mmol, 1 equiv.) in dichloromethane was added N,N-Dimethylformamidedimethyl acetal (CAS No. 4637-24-5, 5.58 mL. 39.5 mmol, 1.5 equiv.). Themixture was heated to reflux for 30 minutes. The reaction was thencooled to room temperature and concentrated under reduced pressure toprovide crude desired product2-bromo-N-(dimethylaminomethylene)propanamide (I-17) as a yellow oil(5.6 g, 98%) which was used as such in the next step.

¹H NMR (400 MHz, CDCl₃) δ ppm: 1.85 (d, J=6.97 Hz, 3H), 3.14 (d, J=0.73Hz, 3H), 3.17 (s, 3H), 4.55 (q, J=6.85 Hz, 1H), 8.49 (s, 1H).

To a solution of 2-bromo-N-(dimethylaminomethylene)propenamide (I-17,5.40 g, 24 mmol, 1 equiv.) in 1,4-dioxane (54 mL) was added5-cyano-2-hydrazinopyridine (CAS No. 104408-24-4, 4.68 g, 25.2 mmol,1.05 equiv.). Next, acetic acid (54 mL) was added slowly. The resultingred solution was heated to 80° C. for 1 hour. The reaction was cooledand concentrated under reduced pressure. The mixture was then taken upin ethyl acetate and washed with a saturated aqueous sodium bicarbonatesolution and water. The organic layer was dried over sodium sulfate,filtered and concentrated under reduced pressure. Purification by flashchromatography over silica gel (ethyl acetate in cyclohexane) affordedthe desired product (I-18) as a white solid (3.1 g, 46%).

¹H NMR (400 MHz, CDCl₃) δ ppm: 2.26 (d, J=6.97 Hz, 3H), 6.43 (q, J=6.97Hz, 1H), 8.05 (s, 1H), 8.14-8.20 (m, 2H), 8.85 (dd, J=1.83, 1.10 Hz,1H).

LC-MS (method 3): retention time 0.88 min, m/z 278-280 (Br pattern)[M+H⁺].

Step C: Preparation of6-[5-[1-[[2-methyl-6,8-bis(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile(compound P.60)

A sealed tube was charged with2-methyl-6,8-bis(trifluoromethyl)quinazolin-4-amine (I-16, 106 mg, 0.36mmol), acetonitrile (1.43 mL), cesium carbonate (351 mg, 1.08 mmol, 3equiv.) and6-[5-(1-bromoethyl)-1,2,4-triazol-1-yl]pyridine-3-carbonitrile (I-18,110 mg, 0.40 mmol, 1.1 equiv.) and the reaction mixture was heated to50° C. for 3 h. The reaction was cooled, diluted with water (60 mL) andextracted three times with ethyl acetate (3×60 mL). The combined organiclayers were washed with brine, dried over sodium sulfate, filtered andconcentrated under reduced pressure. Purification of the crude materialby flash chromatography over silica gel (ethyl acetate in cyclohexane)afforded the desired product as a yellow solid (134 mg, 76% yield).

¹H NMR (400 MHz, DMSO-d6) δ ppm: 1.49-1.58 (m, 3H), 4.09-4.19 (m, 1H),6.49-6.55 (m, 1H), 7.13-7.22 (m, 1H), 7.63-7.71 (m, 1H), 7.83-7.90 (m,1H), 8.17-8.24 (m, 1H), 8.60-8.66 (m, 1H), 9.23-9.29 (m, 1H).

LC-MS (method 3): retention time 1.16 min, m/z 494 [M+H⁺].

Example 8: Preparation of6,8-dichloro-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]quinolin-4-amine(compound P.67)

To a solution of 6,8-dichloroquinolin-4-amine (100 mg, 0.469 mmol) inN,N-dimethylformamide (0.94 mL) was added portionwise at roomtemperature sodium hydride (20.7 mg, 0.516 mmol, 1.10 equiv.). Thereaction mixture was kept stirring at this temperature for 10 minutes. Asolution of 2-[5-(1-bromoethyl)-1,2,4-triazol-1-yl]pyrimidine(intermediate I-20 prepared as described before, 125 mg, 0.493 mmol,1.05 equiv.) in N,N-dimethylformamide (0.94 mL) was then added dropwiseto the reaction mixture and it was stirred at room temperature for 1hour. It was poured into water and extracted three times with ethylacetate. The combined organic layers were washed with brine, dried oversodium sulfate, filtered and concentrated under reduced pressure.Purification of the crude material by flash chromatography over silicagel (ethyl acetate in cyclohexane, then methanol in dichloromethane)afforded the desired product as a pale orange solid (39 mg, 0.10 mmol).

¹H NMR (400 MHz, chloroform-d) δ ppm: 1.75-1.84 (m, 3H) 6.08-6.20 (m,1H) 6.28-6.37 (m, 1H) 6.51-6.58 (m, 1H) 7.45-7.51 (m, 1H) 7.75-7.86 (m,2H) 8.17-8.12 (m, 1H) 8.60-8.66 (m, 1H) 8.94-9.02 (m, 2H).

LC-MS (method 1): retention time 0.63 min, m/z 386-390 [M+H⁺] (dichloropattern).

Example 9: Preparation of6,8-dichloro-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]quinazolin-4-amine(compound P.68)

Step A: Preparation of 2-[5-(1-bromoethyl)-1,2,4-triazol-1-yl]pyrimidine(intermediate I-20)

To a solution of 2-bromopropanamide (CAS 5875-25-2, 1.50 g, 9.38 mmol)in dichloromethane (37.5 mL) was added at room temperature1,1-dimethoxy-N,N-dimethyl-methanamine (CAS 4637-24-5, 2.49 mL, 18.8mmol, 2.00 equiv.). The reaction mixture was heated up to 40° C. andstirred for 2.5 hours. After cooling down to room temperature, thereaction mixture was concentrated under reduced pressure to affordquantitatively crude intermediate (I-19).

LC-MS (method 1): retention time 0.26 min, m/z 207-209 [M+H⁺] (Brpattern).

A mixture of intermediate I-1 (1.94 g, 9.38 mmol), acetic acid (28.1 mL)and pyrimidin-2-ylhydrazine (1.24 g, 11.3 mmol, 1.20 equiv.) was heatedup to 65° C. and stirred for 2 hours. After cooling down to roomtemperature, the reaction mixture was concentrated under reducedpressure. Purification of the crude material by flash chromatographyover silica gel (ethyl acetate in cyclohexane) afforded the desiredproduct (I-20) as a pale yellow solid (1.70 g, 6.69 mmol).

¹H NMR (400 MHz, chloroform-d) δ ppm: 2.20-2.31 (m, 3H) 6.34-6.48 (m,1H) 7.37-7.45 (m, 1H) 8.05-8.15 (m, 1H) 8.88-8.95 (m, 2H).

LC-MS (method 1): retention time 0.66 min, m/z 254-256 [M+H⁺] (Brpattern).

Step B: Preparation of6,8-dichloro-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]quinazolin-4-amine(compound P.68)

To a solution of 6,8-dichloroquinazolin-4-amine (400 mg, 1.87 mmol) inacetonitrile (7.47 mL) were added at room temperature cesium carbonate(1.83 g, 5.61 mmol, 3.00 equiv.) and2-[5-(1-bromoethyl)-1,2,4-triazol-1-yl]pyrimidine (intermediate I-20prepared as described before, 522 mg, 2.06 mmol, 1.10 equiv.). Thereaction mixture was heated up to 50° C. and stirred overnight. Aftercooling down to room temperature, the reaction mixture was diluted withwater and extracted three times with ethyl acetate. The combined organiclayers were washed with brine, dried over sodium sulfate, filtered andconcentrated under reduced pressure. Purification of the crude materialby flash chromatography over silica gel (ethyl acetate in cyclohexane)afforded the desired product as a yellow solid (351 mg, 0.907 mmol).

LC-MS (method 1): retention time 0.81 min, m/z 387-391 [M+H⁺] (dichloropattern).

Example 10: Preparation ofN-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-5,7-bis(trifluoromethyl)isoquinolin-1-amine(compound P.83)

Step A: Preparation of 2-iodo-3,5-bis(trifluoromethyl)benzonitrile(intermediate I-21)

2-Amino-3,5-bis(trifluoromethyl)benzonitrile (I-7, prepared as inExample 2, 2.19 g, 8.62 mmol, 1 equiv.) was dissolved in diiodomethane(6.9 mL) and acetonitrile (13.8 mL). Isoamylnitrite (2.3 mL, 16.4 mmol,1.9 equiv.) was then added under an argon atmosphere. The reaction wasstirred at 50° C. for 60 minutes, then at 80° C. for another 60 minutes.The reaction was concentrated under reduced pressure and diluted withethyl acetate. The organic layer was washed with brine, dried overmagnesium sulfate, filtered and concentrated under reduced pressure togive a crude mixture of oil and solid. The oil was purified by flashchromatography over silica gel (ethyl acetate in cyclohexane) and theresulting solid combined with the crude solid material to afford desiredproduct (I-21) (2.2 g, 70%).

¹H NMR (400 MHz, CDCl₃) δ ppm: 7.99-8.02 (m, 1H), 8.03-8.07 (m, 1H).

Step B: Preparation of3,5-bis(trifluoromethyl)-2-(2-trimethylsilylethynyl)benzaldehyde(intermediate I-23)

2-iodo-3,5-bis(trifluoromethyl)benzonitrile (I-21 prepared above, 3.52g, 9.64 mmol, 1 equiv.) was dissolved in toluene (72 mL) and thesolution cooled to −78° C. and stirred for 90 minutes. The reaction waswarmed to room temperature and quenched by the slow addition of aqueoushydrochloric solution (1 M, 50 mL). The mixture was extracted with ethylacetate (50 mL) and the combined organic layers were washed with brine,dried over sodium sulfate and concentrated under reduced pressure toafford crude 2-iodo-3,5-bis(trifluoromethyl)benzaldehyde (1-22) whichwas used as such for the next step.2-iodo-3,5-bis(trifluoromethyl)benzaldehyde (1-22 prepared above, 3.5 g,9.51 mmol, 1 equiv.) was dissolved in triethylamine (47.5 mL) under anAr atmosphere. Next, copper(I) iodide (0.073 g, 0.38 mmol, 0.04 equiv.),bis(triphenylphosphine)palladium(II) dichloride (0.135 g, 0.19 mmol,0.02 equiv.) and trimethylsilylacetylene (3.39 mL, 23.8 mmol, 2.5 mmol)were added successively and the mixture was stirred at 80° C. After 17hours, the reaction was cooled, concentrated under reduced pressure andthe material was dissolved in ethyl acetate. The organic layer waswashed twice with dilute aqueous hydrochloric solution (2×20 mL), brineand then filtered and concentrated under reduced pressure. Purificationby flash chromatography over silica gel (ethyl acetate in cyclohexane)afforded desired product (I-23) (1.076 g, 33%).

¹H NMR (400 MHz, CDCl₃) δ ppm: 6.33 (br s, 1H), 7.97 (br s, 1H), 8.33(s, 1H), 8.66 (br s, 1H), 11.57 (br s, 1H).

LC-MS (method 3): retention time 1.34 min, m/z 339 [M+H⁺].

Step C: Preparation of 5,7-bis(trifluoromethyl)isoquinoline(intermediate I-24)

3,5-bis(trifluoromethyl)-2-(2-trimethylsilylethynyl)benzaldehyde (1-23prepared above, 1.075 g, 3.18 mmol, 1 equiv.) was weighed in a microwavetube and ammonia solution (7M in methanol, 10 mL) was added. The tubewas capped and irradiated in a microwave reactor for 15 minutes at 130°C. The solvent was then removed under reduced pressure to afford desiredproduct (I-24) (820 mg, 97%).

¹H NMR (400 MHz, CDCl₃) δ ppm: 7.99-8.10 (m, 1H), 8.26 (s, 1H), 8.53 (s,1H), 8.85 (d, J=6.24 Hz, 1H), 9.50 (s, 1H).

LC-MS (method 3): retention time 1.05 min, m/z 266 [M+H⁺].

Step D: Preparation of 2-oxido-5,7-bis(trifluoromethyl)isoquinolin-2-ium(intermediate I-25)

5,7-bis(trifluoromethyl)isoquinoline (I-24 prepared above, 875 mg, 3.3mmol, 1 equiv.) was taken in acetic acid (5.5 mL) and H₂O₂ (35 wt %)(0.85 mL, 9.9 mmol, 3 equiv.) was added. The mixture was then heated to70° C. After 17 hours, the reaction was cooled and diluted with ethylacetate and water and NaOH (4M) was added until pH 12 was reached. Theorganic layer was washed with brine, dried over sodium sulfate, filteredand concentrated under reduced pressure to afford desired product (I-25)(1.040 g, quantitative).

¹H NMR (400 MHz, CDCl₃) δ ppm: ¹H NMR (400 MHz, Solvent) δ ppm 8.05(brd, J=7.34 Hz, 1H), 8.08 (s, 1H), 8.20 (s, 1H), 8.36 (dd, J=7.52, 1.65Hz, 1H), 8.90 (s, 1H).

LC-MS (method 3): retention time 0.85 min. m/z 282 [M+H⁺].

Step E: Preparation ofN-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-5,7-bis(trifluoromethyl)isoquinolin-1-amine(compound P.83)

To a flask containing 2-oxido-5,7-bis(trifluoromethyl)isoquinolin-2-ium(I-25 prepared above, 50 mg, 0.18 mmol. 1 equiv.) and1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethanamine hydrochloride(prepared analog to WO2019/197468 page 128, 80.6 mg, 0.356 mmol, 2equiv.) dissolved in dichloromethane (0.89 mL) was addedN,N-diisopropylethylamine (0.155 mL, 0.89 mmol, 5 equiv.) andbromotripyrrolidinophosphonium hexafluorophosphate (PyBroP®, 211 mg,0.44 mmol, 2.5 equiv.) and the reaction stirred at room temperature.After 4 hours, more N,N-diisopropylethylamine (0.155 mL, 0.89 mmol, 5equiv.) and bromotripyrrolidinophosphonium hexafluorophosphate (PyBroP®,211 mg, 0.44 mmol, 2.5 equiv.) were added. After 17 hours, the reactionwas filtered and the crude purified by flash chromatography over silicagel (ethyl acetate in cyclohexane) to provide desired product P.38 (30mg, 37%).

¹H NMR (400 MHz, CDCl₃) δ ppm: 1.84 (d, J=6.60 Hz, 3H), 6.15-6.97 (m,1H), 6.56 (quin, J=7.06 Hz, 1H), 7.04 (dd, J=5.69, 2.02 Hz, 1H), 7.44(t, J=4.77 Hz, 1H), 7.63 (br d, J=7.34 Hz, 1H), 7.92 (d, J=6.24 Hz, 1H),7.94 (br s, 1H), 8.10 (s, 1H), 8.41 (s, 1H), 8.98 (d, J=4.77 Hz, 2H).

¹⁹F NMR (377 MHz, CDCl₃) δ ppm: −62.15 (s, 1 F), −61.08 (s, 1 F).

LC-MS (method 3): retention time 1.08 min, m/z 454 [M+H⁺].

Example 11: Preparation of6-[5-[(1R)-1-[[6,8-bis(trifluoromethyl)cinnolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile(compound P. 135) Step A: Preparation of6,8-bis(trifluoromethyl)cinnoline-4-ol (I-26)

1-[2-amino-3,5-bis(trifluoromethyl)phenyl]ethanone (CAS-No.:1805121-99-6, 1.25 g, 4.61 mmol, 1 eq) was dissolved in glacial aceticacid (18.4 ml) and Sulfuric acid 70% (0.92 ml, 12.1 mmol, 2.63 eq). Thesolution was cooled to 22° C. and a ice cold solution of sodium nitrite(389 mg, 5.53 mmol, 1.2 eq) in water (3.55 ml) was added dropwise undercooling. After 45 min Triethylamine (1.81 ml, 12.91 mmol, 2.8 eq) wasadded and the reaction was stirred at room temperature for 17 h. It waspoured on 100 ml ice water and it was extracted with Ethylacetate (2×60ml). The combined organic layer was washed saturated Na₂CO₃-solution andbrine, it was dried over anhydrous MgSO₄ and concentrated under reducedpressure. Purification by flash chromatography over silica gel (ethylacetate in cyclohexane) afforded desired product (I-26) (907 mg, 63%).

¹H NMR (400 MHz, CDCl₃) δ ppm: 10.32 (br s, 1H) 8.79 (s, 1H) 8.21 (s,1H) 7.99 (s, 1H).

¹⁹F NMR (377 MHz, CDCl₃) δ ppm: −60.61 (s, 3F) −62.65 (s, 3F).

LC-MS (method 3) retention time 0.88 min m/z 283 [M+H⁺].

Step B: Preparation of 4-chloro-6,8-bis(trifluoromethyl)cinnoline (I-27)

6,8-bis(trifluoromethyl)cinnolin-4-ol (I-26, 840 mg, 2.98 mmol, 1 eq)was suspended in Toluene (5.95 ml) and Phosphoryl trichloride (0.31 ml,3.28 mmol, 1.1 eq) was added. The mixture was heated to 50° C. for 17 h.The reaction was quenched with sat. Ammonium chloride solution anddiluted with Ethylacetate. The pH was adjusted with aqueous Ammonia to10-12. The organic layer was washed five times with brine. It was driedover anhydrous MgSO₄ and concentrated under reduced pressure to give(1-27) (1.04 g, 93% yield, 80% purity).

¹H NMR (400 MHz, CDCl₃) δ ppm: 9.67 (s, 1H) 8.78 (s, 1H) 8.43 (s, 1H).

¹⁹F NMR (377 MHz, CDCl₃) δ ppm: −59.6 (s, 3F) −63.4 (s, 3F).

LC-MS (method 3) retention time 1.11 min m/z 301 [M+H⁺].

Step C: Preparation of(2S)-2-[[6,8-bis(trifluoromethyl)cinnoline-4-yl]amino]propenamide (I-28)

4-chloro-6,8-bis(trifluoromethyl)cinnoline (I-27, 1.04 g, 3.46 mmol, 1eq), Potassium carbonate (2.39 g, 17.3 mmol, 5 eq) and(2S)-2-aminopropanamide;hydrochloride (2.22 g, 17.3 mmol, 5 eq) wereheated to 50° C. in NMP (13.8 ml) for 60 h. The reaction mixture wasdiluted with water (100 ml) and Ethyl acetate (100 ml). The organiclayer was washed with water (30 ml), brine (30 ml), dried with anhydrousNa₂SO₄ and concentrated under reduced pressure to yield (I-28) (1.57 g,73%)

¹H NMR (400 MHz, DMSO-d6) δ ppm: 9.35 (s, 1H) 8.78 (s, 1H) 8.38-8.19 (m,2H) 7.76 (s, 1H) 7.29 (s, 1H) 4.41 (quin, J=7.0 Hz, 1H) 1.56 (d, J=7.0Hz, 3H)

¹⁹F NMR (377 MHz, DMSO-d6) δ ppm: −58.9 (s, 3F) −60.9 (s, 3F) LC-MS(method 3): retention time 0.86 min, m/z 353 [M+H⁺].

Step D: Preparation of(NE,2S)-2-[[6,8-bis(trifluoromethyl)cinnolin-4-yl]amino]-N-(dimethylaminomethylene)propenamide(I-29)

(2S)-2-[[6,8-bis(trifluoromethyl)cinnolin-4-yl]amino]propenamide (I-28,500 mg, 1.42 mmol, 1 eq) was mixed with 2-Methyltetrahydrofuran (14.2ml) and DMF-DMA (377 μl, 2.84 mmol, 2 eq) and heated to 50° C. for 30min. The reaction mixture was evaporated under reduced pressure to yield(I-29) (642 mg, 99%).

LC-MS (method 3): retention time 0.92 min, m/z 408 [M+H⁺].

Step E: Preparation of6-[5-[(1R)-1-[[6,8-bis(trifluoromethyl)cinnolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile(compound P. 135)

(NE,2S)-2-[[6,8-bis(trifluoromethyl)cinnolin-4-yl]amino]-N-(dimethylaminomethylene)propenamide(I 29, 306 mg, 0.75 mmol, 1 eq) was dissolved in 2-Methyltetrahydrofuran(3 ml). 6-Hydrazinylnicotinonitrile (191 mg, 1.35 mmol, 1.8 eq) andacetic acid (1.88 ml) were added. The mixture was heated to 70° C. for 1h. It was cooled to 25° C. and it was diluted with Ethylacetat (30 ml).It washed with water, saturated Na₂CO₃-solution and brine, it was driedover anhydrous Na₂SO₄ and concentrated under reduced pressure.Purification by flash chromatography over silica gel (ethyl acetate incyclohexane), followed by reverse-phase purification (acetonitrile inwater) afforded the desired product (P. 135) (87 mg, 24%).

¹H NMR (400 MHz, CDCl₃) δ ppm: 9.03-8.99 (m, 2H) 8.94 (br s, 1H) 8.30(s, 1H), 8.27-8.23 (m, 2H) 8.06 (s, 1H) 6.44 (q, J=6.6 Hz, 1H) 1.95 (d,J=6.6 Hz, 3H).

¹⁹F NMR (377 MHz, CDCl₃) δ ppm: −60.14 (s, 3F) −62.78 (s, 3F).

LC-MS (method 3): retention time 1.01 min, m/z 480 [M+H⁺].

Example 12: Preparation of4-[[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]amino]-6,8-bis(trifluoromethyl)quinoline-3-carbonitrile(compound P.139)

Step A: Preparation of Ethyl(Z)-3-[2,4-bis(trifluoromethyl)anilino]-2-cyano-prop-2-enoate (compoundI-30)

A mixture of Ethyl (ethoxymethylene)cyanoacetate (1.46 g, 8.47 mmol, 2eq) and 2,4-Bis(trifluoromethyl)aniline (1 g, 4.23 mmol, 1 eq) washeated to 140° C. for 1 h. The mixture was cooled to 25° C. and it waswashed with a mixture of TBME: Cyclohexane 30:70. The solid was filteredoff and dried to give (1-30) (490 mg, 33%).

¹H NMR (400 MHz, DMSO-d6) δ ppm: 11.34 (br d, J=12.5 Hz, 1H) 8.82 (d,J=12.4 Hz, 1H) 810-8.18 (m, 2H) 8.05 (s, 1H) 4.28 (q, J=7.2 Hz, 2H) 1.28(t, J=7.1 Hz, 3H).

LC-MS (method 4): retention time 1.19 min, m/z 353 [M+H⁺].

Step B: Preparation of4-oxo-6,8-bis(trifluoromethyl)-1H-quinoline-3-carbonitrile (compoundI-31)

Ethyl (Z)-3-[2,4-bis(trifluoromethyl)anilino]-2-cyano-prop-2-enoate(I-30, 500 mg, 1.42 mmol, 1 eq) was heated in Phenyl ether-biphenyleutectic (2.5 ml) to 260° C. for 8 h. After cooling to room temperatureit was diluted with Cyclohexane to precipitate the product. It waswashed with tert-butyl methyl ether and dried under reduced pressure togive (1-31) (180 mg, 41%).

¹H NMR (400 MHz, DMSO-d6) δ ppm: 8.68 (s, 1H) 8.66 (s, 1H) 8.45 (s, 1H).

LC-MS (method 4): retention time 0.95 min, m/z 307 [M+H⁺].

Step C: Preparation of4-chloro-6,8-bis(trifluoromethyl)quinoline-3-carbonitrile (compoundI-32)

4-oxo-6,8-bis(trifluoromethyl)-1H-quinoline-3-carbonitrile (I-31, 600mg, 1.96 mmol, 1 eq) and Thionyl chloride (6 ml, 80.6 mmol, 41 eq) weremixed together with N,N-dimethylformamide (30 μl, 0.39 mmol, 0.2 eq).The mixture was heated to 80° C. for 3 h. It was concentrated underreduced pressure and it was purified by flash chromatography over silicagel (ethyl acetate in cyclohexane) to give (1-32) (423 mg, 66%).

¹H NMR (400 MHz, CDCl₃) δ ppm: 9.24 (s, 1H) 8.86 (s, 1H) 8.47 (s, 1H).

LC-MS (method 4): retention time 1.16 min, m/z 325 [M+H⁺].

Step D: Preparation of tert-butylN-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]carbamate(compound I-33)

tert-butyl N-[(1S)-2-amino-1-methyl-2-oxo-ethyl]carbamate (70 g, 353mmol, 1 eq) was mixed with 2-Methyltetrahydrofuran (1.121) and DMF-DMA(70 ml, 530 mmol, 1.5 eq) and heated to 40° C. for 2 h. The reactionmixture was concentrated under reduced pressure to yield (I-33) (105 g,97% yield, 80% purity).

¹H NMR (400 MHz, CDCl₃) δ ppm: 8.38 (s, 1H) 5.98-6.15 (m, 1H) 4.25-4.37(m, 1H) 3.16 (s, 3H) 3.09 (s, 3H) 1.46 (s, 9H) 1.40 (m, 3H).

Step E: Preparation ofN-[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]carbamate(compound I-34)

Tert-butylN-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]carbamate(I-33, 80% purity, 50 g, 164 mmol, 1 eq) was dissolved in 1,4-Dioxane(510 ml). To this was added 6-hydrazinopyridine-3-carbonitrile (33.1 g,247 mmol, 1.5 eq) and glacial acetic acid (510 ml). The mixture washeated to 90° C. for 30 min. After cooling to 25° C. the reactionmixture was concentrated under reduced pressure. Purification by flashchromatography over silica gel (ethyl acetate in cyclohexane) gave(I-34) (23 g, 32%)

¹H NMR (400 MHz, CDCl₃) δ ppm: 8.80 (dd, J=1.90, 0.8 Hz, 1H) 8.10-8.20(m, 1H) 7.98 (s, 1H) 5.92-6.02 (m, 1H) 5.77 (br d, J=8.6 Hz, 1H) 4.12(q, J=7.1 Hz, 2H) 1.58 (d, J=6.8 Hz, 3H) 1.42 (s, 6H).

Step F: Preparation of[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]ammonium;2,2,2-trifluoroacetate(compound I-35)

Tert-butylN-[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]carbamate(I-34, 1.1 g, 3.5 mmol, 1 eq) was dissolved in Methanol (11 ml) andTrifluoroacetic acid (5.6 ml, 70 mmol, 20 eq) was added. The mixture wasstirred at 25° C. for 2 h. The reaction mixture was concentrated underreduced pressure. MTBE was added to the crude oil and it was stirred for5 min. The MTBE was decanted and second time MTBE was added. The productprecipitated out, it was filtered off and dried to yield (I-35) (600 mg,50%).

LC-MS (method 5): retention time 0.31 min, m/z 215 [M+H⁺].

Step G: Preparation of4-[[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]amino]-6,8-bis(trifluoromethyl)quinoline-3-carbonitrile(compound P.139)

In a round bottom flask[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]ammonium;2,2,2-trifluoroacetate(I-34, 546 mg, 1.66 mmol, 1.2 eq),4-chloro-6,8-bis(trifluoromethyl)quinoline-3-carbonitrile (I-32, 450 mg,1.3863 mmol, 1 eq) and Potassium carbonate (581 mg, 4.16 mmol, 3 eq)were suspended in Acetonitrile (9 ml). The reaction mass were heated to60° C. for 2 h. The reaction mass was quenched with water and stirredfor 20 min. P. 139 (432 mg, 62%) precipitated as a solid which wasfiltered, washed with water and was dried under reduced pressure.

¹H NMR (400 MHz, DMSO-d6) δ ppm 9.30 (s, 1H) 8.95 (d, J=7.8 Hz, 1H)8.89-8.93 (m, 1H) 8.73 (s, 1H) 8.49 (dd, J=8.6, 2.1 Hz, 1H) 8.35 (s, 1H)8.31 (s, 1H) 8.07 (d, J=8.7 Hz, 1H) 6.58 (t, J=7.1 Hz, 1H) 1.91 (d,J=6.6 Hz, 3H).

¹⁹F NMR (377 MHz, DMSO-d6) δ ppm −59.16 (s, 3F), −60.26 (s, 3F).

LCMS (method 4): retention time: 1.18 min, m/z 503 [M+H⁺].

Example 13: Preparation of6-chloro-N-methyl-8-(trifluoromethyl)-N-[(1S)-1-[2-[5-[4-(trifluoromethyl)thiazol-2-yl]-2-pyridyl]-1,2,4-triazol-3-yl]ethyl]quinazolin-4-amine(compound P. 142)

Step A: Preparation of6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile(I-36)

A flask was charged with 4,6-dichloro-8-(trifluoromethyl)quinazoline(CAS-No.: 1565368-05-9, 100 mg, 0.37 mmol, 1 eq),[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]ammonium;2,2,2-trifluoroacetate(I-35 from example 12, 74% purity, 199 mg, 0.45 mmol, 1.2 eq), cesiumcarbonate (366 mg, 1.12 mmol, 3 eq) and acetonitrile (1 ml). Thereaction mass was stirred at 25° C. for 16 h. It was diluted with waterand extracted with two times with ethyl acetate. The combined organiclayer was washed with brine, dried aver anhydrous Na₂SO₄ andconcentrated under reduced pressure. The crude material was purified byflash chromatography over silica gel (ethyl acetate in cyclohexane) toprovide desired product (I-36). (107 mg, 64%).

¹H NMR (400 MHz, DMSO-d6) δ ppm: 9.11 (d, J=6.9 Hz, 1H) 9.04 (d, J=1.5Hz, 1H) 8.98-9.00 (m, 1H) 8.93 (d, J=2.2 Hz, 1H) 8.57 (dd, J=8.6, 2.2Hz, 1H) 8.34 (s, 1H) 8.18-8.23 (m, 2H) 8.06-8.10 (m, 1H) 6.37 (t, J=6.85Hz, 1H) 1.74 (, J=7.0 Hz, 3H).

LCMS (method 4): retention time: 1.07 min. m/z 445 [M+H⁺].

Step B: Preparation of6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile(I-37)

6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile(I-36, 1.40 g, 3.15 mmol, 1 eq) was weighed in a sealable tube togetherwith Acetonitrile (15.7 ml), cesium carbonate (3.08 g, 9.44 mmol, 3 eq)and iodomethane (396 μl, 6.29 mmol, 2 eq). The tube was closed andheated to 50° C. for 16 h. After cooling to 25° C. it was extracted twotimes with ethyl acetate. It was washed with water and brine, dried overanhydrous MgSO₄ and concentrated under reduced pressure. It was purifiedby flash chromatography over silica gel (ethyl acetate indichloromethane 3:1) to give (1-37).

¹H NMR (600 MHz, DMSO-d6) δ ppm 8.50 (dd, J=8.5, 2.20 Hz, 1H) 8.45 (s,2H) 8.32 (s, 1H) 8.32 (s, 1H) 8.22 (d, J=1.9 Hz, 1H) 8.09 (d, J=2.1 Hz,1H) 8.05 (d, J=8.5 Hz, 1H) 6.67 (q, J=6.9 Hz, 1H) 3.26 (s, 3H) 1.83 (d,J=6.9 Hz, 3H).

LCMS (method 3): retention time: 1.08 min, m/z 459 [M+H⁺].

Step C: Preparation of6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl].methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyridine-2-carbothioamide(I-38)

To a solution of6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile(I-37, 600 mg, 1.31 mmol, 1 eq) in Pyridine (4.8 ml) was added ammoniumsulfide solution in water (2.23 ml, 6.54 mmol, 5 eq). It was stirred for16 h at 25° C. It was diluted with water and extracted three times withethyl acetate. The combined organic layer was washed brine, dried overanhydrous Na₂SO₄ and concentrated under reduced pressure. It waspurified by flash chromatography over silica gel (ethyl acetate incyclohexane) to give (1-38) (468 mg, 73%).

¹H NMR (400 MHz, DMSO-d6) δ ppm 10.06 (br s, 1H) 9.66 (br s, 1H) 8.44(s, 1H) 8.40 (s, 1H) 8.41 (d, J=7.4 Hz, 2H) 8.27 (s, 1H) 8.17 (d, J=2.0Hz, 1H) 8.05 (d, J=2.1 Hz, 1H) 7.89 (d, J=8.0 Hz, 1H) 6.68 (d, J=7.0 Hz,1H) 3.26 (s, 3H) 1.83 (d, J=7.0 Hz, 3H).

¹⁹F NMR (377 MHz, DMSO-d6) δ ppm −59.39 (s, 3F).

LCMS (method 4): retention time: 1.10 min, m/z 493 [M+H⁺].

Step D: Preparation of2-[6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazol-1-yl]-3-pyridyl]-4-(trifluoromethyl)-5H-thiazol-4-ol(I-39)

6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl].methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyridine-2-carbothioamide(I-38, 100 mg, 0.20 mmol, 1 eq) was dissolved in N,N-Dimethylformamide(2.5 ml). To the solution was added 3-Bromo-1,1,1-trifluoroacetone (32.2μl, 0.30 mmol, 1.5 eq) and it was heated to 60° C. for 2 h. It wascooled to 25° C. and it was diluted with ethyl acetate. It was washedwith water and brine, dried over anhydrous Na₂SO₄ and it wasconcentrated under reduced pressure.

It was purified by flash chromatography over silica gel (ethyl acetatein cyclohexane) to give (1-39) (103 mg, 76%, 90% purity).

¹H NMR (400 MHz, Acetonitrile-d3) δ ppm: 8.52 (d, J=4.4 Hz, 1H) 8.32(ddd J=12.2, 8.6, 2.3 Hz) 8.07-8.15 (m, 1H) 8.06-8.12 (m, 1H), 8.03 (s,1H) 7.95 (dd, J=8.6, 5.1 Hz, 1H) 7.8 (d, J=2.3 Hz, 1H) 7.73 (d, J=2.2Hz, 1H) 6.76 (t, J=7.6 Hz, 1H) 5.05 (br dd, J=16.7, 2.6 Hz, 1H) 3.78(dd, J=13.0 Hz, 10.8 Hz, 1H) 3.61 (s, 1H) 3.47-3.55 (m, 1H) 3.12 (d,J=7.5 Hz, 3H) 2.09-2.21 (m, 5H) 1.87 (dd, J=6.9, 1.3 Hz, 3H).

LCMS (method 4): retention time: 1.17 min, m/z 604 [M+H⁺].

Step E: Preparation of6-chloro-N-methyl-8-(trifluoromethyl)-N-[(1S)-1-[2-[5-[4-(trifluoromethyl)thiazol-2-yl]-2-pyridyl]-1,2,4-triazol-3-yl]ethyl]quinazolin-4-amine(compound P. 142)

To a solution of2-[6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazol-1-yl]-3-pyridyl]-4-(trifluoromethyl)-5H-thiazol-4-ol(I-39, 100 mg, 0.17 mmol, 1 eq) in Tetrahydrofuran (4 ml) was addedTriethylamine (58.4 μl, 0.41 mmol, 2.5 eq) and it was cooled to 0° C.Trifluoroacetic anhydride (118 μl, 0.83 mmol, 5 eq) was added at 0° C.The reaction mixture was warmed to room temperature and it was stirredfor 16 h. It was quenched with saturated NaHCO₃-solution and it wasextracted with EtOAc (2×20 ml). The combined organic layer was washedwith brine, dried over anhydrous Na₂SO₄ and concentrated under reducedpressure to get gummy mass. The crude material was purified by flashchromatography over silica gel (ethyl acetate in cyclohexane) to providedesired product P. 142 (47 mg, 48% yield).

¹H NMR (400 MHz, DMSO-d6) δ ppm 8.65 (s, 1H) 8.55 (s, 1H) 8.50 (dd,J=8.5, 2.3 Hz, 1H) 8.31 (s, 1H) 8.27-8.30 (m, 1H) 8.06 (s, 1H) 7.97 (d,J=8.3 Hz 1H) 7.85 (s, 1H) 6.65 (br d, J=6.8 Hz, 1H) 3.10 (s, 3H) 1.88(d, J=6.8 Hz, 3H).

¹⁹F NMR (377 MHz, DMSO-d6) δ ppm −59.6 (s, 3 F) −62.5 (s, 3 F).

LCMS (method 4): retention time: 1.26 min, m/z 585 [M+H⁺].

Example 14: Preparation ofN-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)-1,2,3-benzotriazin-4-amine(compound P. 145)

Step A: Preparation of 2-amino-3,5-bis(trifluoromethyl)benzamide (I-40)

2-Amino-3,5-bis(trifluoromethyl)benzonitrile (CAS-No. 473740-86-2, 1.00g, 3.94 mmol, 1 eq) and potassium carbonate (109 mg, 0.79 mmol, 0.2 eq)were dissolved in Methanol (15 ml) and water (2 ml). While stirring at25° C. urea hydrogen peroxide (1.14 g, 11.81 mmol, 3 eq) was added andstirred for 1 h. After that a second batch of urea hydrogen peroxide(1.14 g, 11.81 mmol, 3 eq) was added and stirred for 16 h. Sodiummetabisulfite (1 g) was added and stirred for 5 min. It was diluted withethyl acetate. The solid was filtered off and the filtrate wasconcentrated under reduced pressure. The crude material was purified byflash chromatography over silica gel (ethyl acetate in cyclohexane) toprovide desired product (I-40) (818 mg, 76%).

¹H NMR (400 MHz, DMSO-d6) δ ppm 8.22-8.39 (br s, 1H) 8.18 (s, 1H) 7.78(s, 1H) 7.50-7.70 (br s, 3H).

LCMS (method 3): retention time: 0.91 min, m/z 273 [M+H⁺].

Step B: Preparation of6,8-bis(trifluoromethyl)-3H-1,2,3-benzotriazin-4-one (I-41)

A solution of 2-amino-3,5-bis(trifluoromethyl)benzamide (I-40, 816 mg, 3mmol, 1 eq) in 1N hydrogen chloride (12 ml) was stirred for 20 min at 0°C. A solution of sodium nitrite (414 mg, 6 mmol, 2 eq) in water (10 ml)was added dropwise over 40 min. After that it was stirred for 2 h at 0°C. 4M sodium hydroxide was added to adjust the pH to 8 and it wasvigorously stirred for 15 min. The solid was filtered off and filtratewas acidified to pH 2-3 with HCl. The solid product was filtered off anddried to get (1-41) (382 mg, 45%).

¹H NMR (400 MHz, DMSO-d6) δ ppm 15.56-15.89 (br s, 1H) 8.77 (s, 1H) 8.71(s, 1H).

LCMS (method 3): retention time: 0.92 min, m/z 284 [M+H⁺].

Step C: Preparation of tert-butylN-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]carbamate (I-42)

Tert-butylN-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]carbamate(I-33 from example 12, 4.23 g, 17.4 mmol, 1 eq) pyrimidin2-ylhydrazine(2.87 g, 26.1 mmol, 1.5 eq) was mixed together with 1,4-Dioxane (43.5ml) and glacial acetic acid (43.5 ml). The mixture was heated to 90° C.for 35 min. It was concentrated under reduced pressure and purified withflash column chromatography over silica gel (ethyl acetate incyclohexane) to provide desired product (I-42) (4.03 g, 80%).

¹H NMR (400 MHz, CDCl₃) δ ppm 8.89 (d, J=4.8 Hz, 2H) 8.03 (s, 1H) 7.37(t, J=5.0 Hz, 1H) 5.91-6.11 (m, 1H) 5.55-5-77 (m, 1H) 1.58 (d, J=6.6 Hz,3H) 1.35-1.47 (m, 9H).

LCMS (method 3): retention time: 0.73 min, m/z 291 [M+H⁺].

Step D: Preparation of[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]ammonium;2,2,2-trifluoroacetate(I-43)

tert-butylN-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]carbamate (I-42,36.0 g, 86.6 mmol, 1 eq) was dissolved in Dichloromethane (540 ml) andTrifluoroacetic acid (180 ml, 2.27 mol, 26.2 eq) was added. The mixturewas stirred at 25° C. for 2 h. The reaction mixture was concentratedunder reduced pressure.

Tert-butyl methyl ether (72 ml) was added to the crude oil and it wasstirred for 5 min. The MTBE was decanted off and Acetonitrile (72 ml)was added. The product precipitated out, it was filtered off and driedto yield (I-43) (22.3 g, 83%).

¹H NMR (400 MHz, DMSO-d6) δ ppm 9.02 (d, 2H) 8.55-8.75 (br s, 3H) 8.37(s, 1H) 7.68 (t, 1H) 5.34 (m, 1H) 3.20-4.40 (br s, 1H) 1.63 (d, 3H).

LC-MS (method 5): retention time 0.27 min, m/z 191 [M+H⁺].

Step E: Preparation ofN-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)-1,2,3-benzotriazin-4-amine(compound P. 145)

6,8-bis(trifluoromethyl)-3H-1,2,3-benzotriazin-4-one (I-41, 129 mg, 0.45mmol, 1 eq),(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethanamine;2,2,2-trifluoroaceticacid (1-43, 180 mg, 0.59 mmol, 1.3 eq) andN-ethyl-N-isopropyl-propan-2-amine (0.325 ml, 1.86 mmol, 4.1 eq) weredissolved in Dimethylsulfoxide (4.5 ml).

After stirring for 5 min at room temperaturebenzotriazol-1-yloxy(tripyrrolidin-1-yl)phosphonium;hexafluorophosphate(662 mg, 1.27 mmol, 2.8 eq) The resulting mixture was stirred for 16 hat room temperature. It was diluted with water (50 ml) and it wasextracted with EtOAc (3×50 ml). The combined organic layer was driedover anhydrous Na₂SO₄ and concentrated under reduced pressure.Purification by flash chromatography over silica gel (ethyl acetate incyclohexane) afforded desired product (P. 145) (68 mg, 33% yield).

¹H NMR (400 MHz, DMSO-d6) δ ppm 9.64 (d, J=7.0 Hz, 1H) 9.34 (s, 1H) 8.98(d, J=4.8 Hz, 2H) 8.61 (s, 1H) 8.17 (s, 1H) 7.64 (t, J=5.0 Hz, 1H) 6.57(m, 1H) 1.82 (d, J=7.0 Hz, 3H).

¹⁹F NMR (377 MHz, DMSO-d6) δ ppm −58.5 (s, 3 F) −61.2 (s, 3 F).

LC-MS (method 3) retention time 0.92 min, m/z 456 [M+H⁺].

Example 15: Preparation of3-fluoro-N-methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinolin-4-amine(compound P.176)

Step A: Preparation ofN-methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinolin-4-amine(I-44)

A dry vial was charged with sodium hydride (60 mass %, 13.2 mg, 0.33mmol, 1.5 eq) and cooled to 0° C. To this was added a solution ofN-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinolin-4-amine(P. 5 example 1, 100 mg, 0.22 mmol, 1 eq) in Tetrahydrofuran (0.88 ml).After 5 min stirring Iodomethane (20.8 μl, 0.33 mmol, 1.5 eq) was addedand it was stirred at 25° C. for 3.5 h. It was quenched with sat.NH₄Cl-solution (5 ml) and diluted with water (20 ml). It was extractedwith ethyl acetate (3×20 ml). The combined organic layer was washedbrine, dried over anhydrous Na₂SO₄ and concentrated under reducedpressure. Purification by flash chromatography over silica gel (ethylacetate in cyclohexane) afforded desired product (I-44) (41 mg, 40%).

¹H NMR (400 MHz, CDCl₃) δ ppm 8.65 (d, J=5.1 Hz, 1H) 8.43 (s, 1H) 8.20(d, J=1.1 Hz, 1H) 8.09 (s, 1H) 8.08 (d, J=4.8 Hz, 2H) 6.93 (t, J=4.8 Hz,1H) 6.68 (d, J=5.1 Hz, 1H) 6.25 (q, J=7.0 Hz, 1H) 2.88 (s, 3H) 2.08 (d,J=7.0 Hz, 3H).

LC-MS (method 3) retention time 1.04 min, m/z 468 [M+H⁺].

Step B: Preparation of3-fluoro-N-methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinolin-4-amine(compound P.176)

N-methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinolin-4-amine(30 mg, 0.064 mmol, 1 eq) was dissolved in Acetonitrile (321 μl).Selectfluor (23.7 mg, 0.064 mmol, 1 eq) was added and it was stirred atroom temperature for 17 h. A second batch of Selectfluor (12 mg, 0.032mmol, 0.5 eq) was added and stirred for additional 7 h. A third batch ofSelectfluor (12 mg, 0.032 mmol, 0.5 eq) was added and stirred for 17 h.It was quenched with MeOH, filtered and purified on RP18 silica. P. 176(18 mg, 58% yield).

¹H NMR (400 MHz, CDCl₃) δ ppm 8.68 (d, J=3.7 Hz, 1H) 8.51 (s, 1H) 8.15(s, 3H) 8.11 (s, 1H) 6.91 (t, J=4.8 Hz, 1H) 6.03 (q, J=7.0 Hz, 1H) 3.09(d, J=3.7 Hz, 3H) 2.02 (d, J=7.0 Hz, 3H).

¹⁹F NMR (377 MHz, CDCl₃) δ ppm −60.52 (s, 3 F) −62.51 (s, 3 F) −133.71(s, 1 F).

LC-MS (method 3) retention time 1.10 min, m/z 487 [M+H⁺].

Example 16: Preparation of3-chloro-N-methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinolin-4-amine(P. 181)

Step A: Preparation of3-chloro-N-methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinolin-4-amine(compound P. 181)

N-methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinolin-4-amine(I-44 example 15, 41 mg, 0.088 mmol, 1 eq) was dissolved inDichloromethane (0.88 ml) and cooled to −19° C. N-Chlorosuccinimide (13mg, 0.096 mmol, 1.1 eq) was added and stirred for 1 h at −19° C. Afterthat it was stirred for 20 h at room temperature. AdditionalN-Chlorosuccinimide (13 mg, 0.096 mmol, 1.1 eq) and Dimethylsulfoxide(31.5 μl) were added. After 17 h full conversion. It was concentratedunder reduced pressure and purified by flash chromatography over silicagel (ethyl acetate in cyclohexane) afforded desired product P.181 (14mg, 32% yield).

¹H NMR (600 MHz, DMSO-d6, 120° C.) δ ppm 8.86 (s, 1H) 8.41 (d, J=4.7 Hz,2H) 8.24 (s, 1H) 8.13 (s, 1H) 7.24 (t, J=4.8 Hz, 1H) 5.91 (q, J=7.0 Hz,1H) 3.15 (s, 3H) 1.86 (d, J=6.9 Hz, 3H).

LC-MS (method 3) retention time 1.14 min, m/z 502 [M+H⁺].

Example 17: Preparation of6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbothioamide(P. 190)

Step A: Preparation of6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile(I-45)

Tert-butylN-[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]carbamate(I-34, 75% purity, 13 g, 31 mmol, 1 eq) was dissolved in Dichloromethane(195 ml) and Trifluoroacetic acid (78 ml, 982 mmol, 31.7 eq) was added.The mixture was stirred at 25° C. for 1 h. The reaction mixture wasconcentrated under reduced pressure.

Dichloromethane (195 ml) was added to the crude oil and it was basifiedwith saturated Na₂CO₃-solution. The aqueous layer was extracted withdichloromethane (2×200 ml). The combined organic layer was dried overanhydrous Na₂SO₄ and concentrated under reduced pressure to give a whitesolid. This was washed TBME and was dried under reduced pressure to give(1-45) (7 g, 87%, 88% purity).

¹H NMR (400 MHz, DMSO-d6) δ ppm 9.06 (s, 1H) 8.55 (d, 1H) 8.23 (s, 1H)8.06 (d, 1H) 4.67-4.87 (m, 1H) 1.47 (d, 3H).

Step B: Preparation of6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile(I-46)

4-chloro-6,8-bis(trifluoromethyl)quinazoline (I-9 example 2, 4.0 g, 13.3mmol, 1 eq) was dissolved in acetonitrile (40 ml).6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile(I-45, 85% purity, 3.35 g, 13.3 mmol, 1 eq) and cesium carbonate (8.67g, 26.6 mmol, 2 eq) were added and it was stirred at 25° C. for 16 h.The reaction mixture was poured on ice-water and it was extracted withethyl acetate (3×50 ml). The combined organic layer was dried overanhydrous Na₂SO₄ and concentrated under reduced pressure followed bypurification by flash chromatography over silica gel (ethyl acetate incyclohexane) to afford desired product (I-46) (5.1 g, 80%).

¹H NMR (400 MHz, DMSO-d6) δ ppm 9.47 (d, 1H) 9.27 (s, 1H) 9.04 (s, 1H)8.58 (d, 1H) 8.44 (s, 1H) 8.36 (s, 1H) 8.21 (s, 1H) 8.09 (d, 1H) 6.42(quin., 1H) 1.77 (d, 3H).

LC-MS (method 5) retention time 1.59 min, m/z 479 [M+H⁺].

Step C: Preparation of6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile(I-47)

A sealable tube was charged with6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile(I-46, 294 mg, 0.61 mmol, 1 eq), acetonitrile (4.92 ml), cesiumcarbonate (601 mg, 1.84 mmol, 3 eq) and iodomethane (77.3 μl, 1.23 mmol,2 eq). The vial was sealed and heated to 50° C. for 16 h. After coolingto 25° C. it was diluted with water (10 ml) and it was extracted withethyl acetate (3×10 ml). The combined organics were washed with brine,dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. Itwas purified by flash chromatography over silica gel (ethyl acetate incyclohexane) and afforded desired product (I-47) (250 mg, 83%).

¹H NMR (400 MHz, CDCl₃) δ ppm 8.55 (s, 1H) 8.35 (d, J=5.9 Hz, 2H) 8.24(s, 1H) 8.11-8.20 (m, 2H) 8.03 (s, 1H) 6.88 (q, J=6.97 Hz, 1H) 1.96 (d,J=6.97 Hz, 3H).

¹⁹F NMR (377 MHz, CDCl₃) δ ppm −61.33 (s, 3F) −62.39 (s, 3F).

LC-MS (method 3) retention time 1.11 min, m/z 493 [M+H⁺].

Step D: Preparation of6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbothioamide(P. 190)

6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile(I-47, 300 mg, 0.61 mmol, 1 eq) was dissolved in Pyridine (2.4 ml) andammonium sulfide solution (20 mass %, 1.04 ml, 3.05 mmol, 5 eq) wasadded. The reaction mixture was stirred at 25° C. for 16 h. It wasdiluted with water and it was extracted with ethyl acetate (4 times).The combined organic layer was washed with brine, dried over anhydrousNa₂SO₄ and concentrated under reduced pressure. It was purified by flashchromatography over silica gel (ethyl acetate in cyclohexane) to give(P. 190) (78 mg, 24%).

¹H NMR (400 MHz, DMSO-d6) δ ppm 10.04 (br s, 1H) 9.65 (br s, 1H) 8.55(s, 1H) 8.27-8.41 (m, 5H) 7.91 (d, J=8.44 Hz, 1H) 6.76 (br d, J=6.85 Hz,1H).

¹⁹F NMR (377 MHz, DMSO-d6) δ ppm −59.74 (s, 3F) −60.75 (s, 3F).

LC-MS (method 4) retention time 1.12 min. m/z 528 [M+H⁺].

TABLE P Examples of compounds of formula I RT [M + H] Entry IUPAC nameSTRUCTURE (min) (measured) Method MP° C. P.1 N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethyl]-6,8- bis(trifluoromethyl)quina-zolin-4-amine

0.96 455 3 130- 132 P.2 6,7,8-trichloro-N-methyl- N-[1-(3-pyrimidin-2-ylpyrazin-2- yl)ethyl]quinazolin-4- amine

0.98 448 3 P.3 6,7,8-trichloro-N-[1-[3- (triazol-2-yl)pyrazin-2-yl]ethyl]quinazolin-4- amine

0.99 423 3 P.4 N-[1-(5-bromo-2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-N- methyl-6,8- bis(trifluoromethyl)quina-zolin-4-amine

1.14 547-549 (Br pattern) 3 P.5 N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethyl]-6,8- bis(trifluoromethyl)quino-lin-4-amine

0.89 455 3 P.6 6-[5-[1-[[6,8- bis(trifluoromethyl)quina-zolin-4-yl]-ethyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3-carbonitrile

1.17 507 3 P.7 6-[5-[1-[[6,8- bis(trifluroomethyl)quina- zolin-4-yl]-(methoxymethyl)amino] ethyl]-1,2,4-triazol-1- yl]pyridine-3-carbonitrile

1.13 523 3 P.8 6-[5-[1-[benzyl-[6,8- bis(trifluoromethyl)quina-zolin-4-yl]amino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile

1.21 569 3 P.9 [6,8- bis(trifluoromethyl)quina- zolin-4-yl]-[1-[2-(5-cyano-2-pyridyl)-1,2,4- triazol-3- yl]ethyl]cyanamide

1.10 504 3 P.10 benzyl N-[6,8- bis(trifluoromethyl)quina-zolin-4-yl]-N-[1-[2-(5- cyano-2-pyridyl)-1,2,4- triazol-3-yl]ethyl]carbamate

1.18 613 3 P.11 6-bromo-N-[1-(3- pyrimidin-2-ylpyrazin-2- yl)ethyl]-8-(trifluoromethoxy)quina- zolin-4-amine

0.92 492-494 (Br pattern) 3 P.12 8-bromo-N-[1-(3-pyrimidin-2-ylpyrazin-2- yl)ethyl]-6- (trifluoromethoxy)quina-zolin-4-amine

0.92 492-494 (Br pattern) 3 238- 239 P.13 8-bromo-N-[1-[3-(triazol-2-yl)pyrazin-2-yl]ethyl]- 6- (trifluoromethoxy)quina- zolin-4-amine

1.00 481-483 (Br pattern) 3 P.14 6-bromo-N-[1-[3-(triazol-2-yl)pyrazin-2-yl]ethyl]- 8- (trifluoromethoxy)quina- zolin-4-amine

0.99 481-483 (Br pattern) 3 P.15 6-[5-[1-[methyl-[2- methyl-6,8-bis(trifluoromethyl)quina- zolin-4-yl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3-carbonitrile

1.20 507 3 155- 158 P.16 N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]- 6,8- bis(trifluoromethyl)quina- zolin-4-amine

0.97 455 3 192- 194 P.17 6-[5-[(1S)-1-[[8-chloro-6-(trifluoromethyl)quinazolin- 4-yl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3-carbonitrile

0.99 445 3 P.18 8-chloro-N-[(1S)-1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6- (trifluoromethyl)quinazolin- 4-amine

1.43 421 5 P.19 6-[5-[(1S)-1-[[8-chloro-6- (trifluoromethyl)quinazolin-4-yl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3- carbonitrile

1.02 459 3 196- 198 P.20 8-chloro-N-methyl-N- [(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethyl]-6- (trifluoromethyl)quinazolin- 4-amine

1.42 435 5 138- 140 P.21 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin- 4-yl]-methyl- amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbonitrile

1.08 459 3 94-96 P.22 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin- 4-yl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3-carbonitrile

1.04 445 3 236- 238 P.23 6-chloro-N-methyl-N- [(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethyl]-8- (trifluoromethyl)quinazolin- 4-amine

0.96 435 3 82-84 P.24 6-chloro-N-[(1S)-1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-8- (trifluoromethyl)quinazolin- 4-amine

0.91 421 3 234- 236 P.25 2-chloro-N-[1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8- bis(trifluoromethyl)quina- zolin-4-amine

1.09 489 4 188- 190 P.26 N-methyl-N-[(1S)-1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8- bis(trifluoromethyl)quina- zolin-4-amine

1.01 469 3 160- 163 P.27 N-methyl-N-[1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8- bis(trifluoromethyl)quina- zolin-4-amine

1.01 469 3 P.28 6-[5-[1-[[6,8- bis(trifluoromethyl)quina-zolin-4-yl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3-carbonitrile

1.11 493 3 P.29 6,8-dibromo-N-[1-(2- pyrimidin-2-yl-1,2,4- triazol-3-yl)ethyl]quinazolin-4- amine

0.85 473-478 (dibromo pattern) 3 138- 145 P.30 6-[5-[1-[(6,8-dibromoquinazolin-4- yl)amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3-carbonitrile

0.98 499-504 (dibromo pattern) 3 167- 174 P.31 6-bromo-8-(difluoromethoxy)-N-[1- [3-(triazol-2-yl)pyrazin-2-yl]ethyl]quinazolin-4- amine

0.89 463-465 (Br pattern) 3 154- 155 P.32 6-bromo-8-(difluoromethoxy)-N-[1- (3-pyrimidin-2-ylpyrazin-2-yl)ethyl]quinazolin-4- amine

0.80 474-476 (Br pattern) 3 94-96 P.33 6-bromo-N-[1-[3-(triazol-2-yl)pyrazin-2-yl]ethyl]- 8- (trifluoromethyl)quinazolin- 4-amine

1.07 465-467 (Br pattern) 4 P.34 8-bromo-N-[1-[3-(triazol-2-yl)pyrazin-2-yl]ethyl]- 6- (trifluoromethyl)quinazolin- 4-amine

1.04 465-467 4 240- 242 P.35 8-chloro-N-[1-[3-(triazol-2-yl)pyrazin-2-yl]ethyl]- 6- (trifluoromethyl)quinazolin- 4-amine

1.47 421 5 242- 244 P.36 8-chloro-N- (cyclopropylmethyl)-2-methoxy-N-[1-(2- pyrimidin-2-yl-1,2,4- triazol-3-yl)ethyl]-6-(trifluoromethyl)quinazolin- 4-amine

1.17 505 4 143- 145 P.37 6,8-dibromo-N-[1-[3- (triazol-2-yl)pyrazin-2-yl]ethyl]quinazolin-4- amine

0.96 475-479 (dibromo pattern) 3 164- 173 P.38 6,8-dibromo-N-[1-(3-pyrimidin-2-ylpyrazin-2- yl)ethyl]quinazolin-4- amine

0.87 486-490 (dibromo pattern) 3 156- 163 P.396-chloro-N-[1-[3-(triazol- 2-yl)pyrazin-2-yl]ethyl]- 8-(trifluoromethyl)quinazolin- 4-amine

1.06 421 4 190- 194 P.40 6-chloro-N-[1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-8- (trifluoromethyl)quinazolin- 4-amine

1.42 421 5 198- 200 P.41 6-[5-[1-[[6-chloro-8-(trifluoromethyl)quinazolin- 4-yl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3-carbonitrile

1.56 445 5 P.42 6-[5-[1-[[8-bromo-6- (trifluoromethyl)quinazolin-4-yl]amino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile

1.07 489-491 (Br pattern) 4 P.43 8-chloro-N-[1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6- (trifluoromethyl)quinazolin- 4-amine

0.89 422 4 P.44 6-bromo-N-[1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-8- (trifluoromethyl)quinazolin- 4-amine

0.96 465-467 (Br pattern) 4 208- 212 P.45 6-[5-[1-[[8-chloro-6-(trifluoromethyl)quinazolin- 4-yl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3-carbonitrile

1.58 445 5 P.46 8-bromo-2-chloro-N- (cyclopropylmethyl)-N-[1-(2-pyrimidin-2-yl- 1,2,4-triazol-3-yl)ethyl]- 6-(trifluoromethyl)quinazolin- 4-amine

1.22 553-555 (Br pattern) 4 87-89 P.47 8-bromo-N-[1-(2-pyrimidin-2-yl-1,2,4- triazol-3-yl)ethyl]-6-(trifluoromethyl)quinazolin- 4-amine

0.94 465-467 (Br pattern) 4 P.48 2,8-dichloro-N-[1-(2-pyrimidin-2-yl-1,2,4- triazol-3-yl)ethyl]-6-(trifluoromethyl)quinazolin- 4-amine

1.04 455-459 (dichloro pattern) 4 P.49 2,8-dichloro-N-(cyclopropylmethyl)-N- [1-(2-pyrimidin-2-yl- 1,2,4-triazol-3-yl)ethyl]-6- (trifluoromethyl)quinazolin- 4-amine

1.20 509-5.13 (dichloro pattern) 4 81-83 P.50 6-[5-[1-[(6,7,8-trichloroquinazolin-4- yl)amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3-carbonitrile

1.05 447 9 P.51 8-bromo-2-chloro-N-[1- (2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6- (trifluoromethyl)quinazolin- 4-amine

1.05 499-503 (Cl + Br pattern) 4 P.52 6-[5-[1-[[6-bromo-8-(trifluoromethyl)quinazolin- 4-yl]-methyl- amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbonitrile

1.09 503-505 (Br pattern) 3 149- 152 P.53 6-[5-[(1R)-1-[[6,8-bis(trifluoromethyl)quina- zolin-4-yl]-methyl- amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbonitrile

P.54 6-[5-[(1S)-1-[[6,8- bis(trifluoromethyl)quina- zolin-4-yl]-methyl-amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3- carbonitrile

1.10 493 3 140- 142 P.55 N-[1-[3-(triazol-1- yl)pyrazin-2-yl]ethyl]-6,8- bis(trifluoromethyl)quina- zolin-4-amine

1.08 456 3 P.56 N-[1-[3-(triazol-2- yl)pyrazin-2-yl]ethyl]- 6,8-bis(trifluoromethyl)quina- zolin-4-amine

1.09 456 3 189- 191 P.57 6-[5-[1-[[6,8- bis(trifluoromethyl)quina-zolin-4-yl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3-carbonitrile

1.11 493 3 P.58 N-methyl-N-[1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8- bis(trifluoromethyl)quina- zolin-4-amine

1.01 469 3 P.59 6-[5-[1-[[2,6,8- tris(trifluoromethyl)quina-zolin-4-yl]amino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile

1.20 547 3 P.60 6-[5-[1-[[2-methyl-6,8- bis(trifluoromethyl)quina-zolin-4-yl]amino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile

1.16 494 3 P.61 6-[5-[1-[[6,8- bis(trifluoromethyl)quina-zolin-4-yl]amino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile

1.07 479 3 P.62 6-[5-[1-[[8- (trifluoromethyl)quinazolin-4-yl]amino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile

0.93 411 3 P.63 6-[5-[1-[[6-bromo-8- (trifluoromethyl)quinazolin-4-yl]amino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile

1.05 489-491 (Br pattern) 3 P.64 6-[5-[1-[[6-(trifluoromethyl)quinazolin- 4-yl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3-carbonitrile

0.83 411 3 P.65 6-[5-[1-[(6,8- dichloroquinazolin-4-yl)amio]ethyl]-1,2,4- triazol-1-yl]pyridine-3- carbonitrile

0.96 411-415 (dichloro pattern) 3 P.66 6,8-dichloro-N-methyl-N-[1-(2-pyrimidin-2-yl- 1,2,4-triazol-3- yl)ethyl]quianzolin-4- amine

0.87 401-405 (dichloro pattern) 3 P.67 6,8-dichloro-N-[1-(2-pyrimidin-2-yl-1,2,4- triazol-3- yl)ethyl]quinolin-4-amine

0.63 386-390 (dichloro pattern) 1 P.68 6,8-dichloro-N-[1-(2-pyrimidin-2-yl-1,2,4- triazol-3- yl)ethyl)quinazolin-4- amine

0.81 387-391 (dichloro pattern) 1 P.69 N-[1-[2-(2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-5- (trifluoromethyl)isoquino- lin-1-amine

1.12 385 3 P.70 7-bromo-N-[1-(2- pyrimidin-2-yl-1,2,4- triazol-3-yl)ethyl]isoquinolin-1- amine

0.92 396-398 (Br pattern) 3 P.71 8-bromo-N-methyl-N-[1-(2-pyrimidin-2-yl-1,2,4- triazol-3-yl)ethyl]-6-(trifluoromethyl)quinazolin- 4-amine

0.97 481 4 178- 180 P.72 6-[3-[1-[[8-chloro-6-(trifluoromethyl)quinazolin- 4-yl]- (cyclopropylmethyl)amino]ethyl]pyrazin-2- yl]pyridine-3-carbonitrile

1.28 511 4 81-83 P.73 6-[3-[1-[[8-bromo-6- (trifluoromethyl)quinazolin-4-yl]- (cyclopropylmethyl)amino] ethyl]pyrazin-2-yl]pyridine-3-carbonitrile

1.28 556 4 81-83 P.74 6-[3-[1-[[6-bromo-8- (trifluoromethyl)quinazolin-4-yl]- (cyclopropylmethyl)amino] ethyl]pyrazin-2-yl]pyridine-3-carbonitrile

1.29 556 4 251- 253 P.75 N-(cyclopropylmethyl)- N-[1-[3-(triazol-2-yl)pyrazin-2-yl]ethyl]- 6,8- bis(trifluoromethyl)quina- zolin-4-amine

1.27 510 4 P.76 8-chloro-N- (cyclopropylmethyl)-N- [1-[3-(triazol-2-yl)pyrazin-2-yl]ethyl]-6- (trifluoromethyl)quinazolin- 4-amine

1.21 477 4 110- 112 P.77 6-chloro-N- (cyclopropylmethyl)-N-[1-[3-(triazol-2- yl)pyrazin-2-yl]ethyl]-8- (trifluoromethyl)quinazolin-4-amine

1.24 476 4 P.78 6-bromo-N- (cyclopropylmethyl)-N- [1-[3-(triazol-2-yl)pyrazin-2-yl]ethyl]-8- (trifluoromethyl)quinazolin- 4-amine

1.27 521 4 P.79 6-bromo-N-[1-[2-(5- bromo-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-8- (trifluoromethyl)quinazolin- 4-amine

1.62 544 5 214- 216 P.80 6-bromo-N- (cyclopropylmethyl)-N-[1-(3-pyrimidin-2- ylpyrazin-2-yl)ethyl]-8- (trifluoromethyl)quinazolin-4-amine

1.76 532 5 169- 171 P.81 8-chloro-N- (cyclopropylmethyl)-N-[1-(3-pyrimidin-2- ylpyrazin-2-yl)ethyl]-6- (trifluoromethyl)quinazolin-4-amine

1.67 486 5 64-66 P.82 cyclopropyl-[4-[methyl- [(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethyl]amino]-8- (trifluoromethyl)quinazolin-6-yl]methanone

0.96 470 3 P.83 N-[1-(2-pyrimidin-2-yl- 1,2,4-triazol-3-yl)ethyl]- 5,7-bis(trifluoromethyl)iso- quinolin-1-amine

1.08 454 3 P.84 N-methyl-N-[(1S)-1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-8- (trifluoromethyl)-6- (trifluoromethylsulfanyl)quinazolin-4-amine

1.08 502 3 P.85 N-[1-(3-pyrimidin-2- ylpyrazin-2-yl)ethyl]-6,8-bis(trifluoromethyl)quino- lin-4-amine

0.90 465 3 P.86 6-iodo-N-methyl-N- [(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-o yl)ethyl]-8- (trifluoromethyl)quinazolin- 4-amine

75-80 P.87 6-iodo-N-[(1S)-1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-8- (trifluoromethyl)quinazolin- 4-amine

0.96 513 3 252- 255 P.88 N-methyl-N-[(1S)-1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8- bis(trifluoromethyl)quino- lin-4-amine

1.04 469 3 P.89 N-[1-[2-(5- bromopyrimidin-2-yl)-1,2,4-triazol-3-yl]ethyl]- N-methyl-6,8- bis(trifluoromethyl)quina-zolin-4-amine

1.11 547-549 (Br pattern) 3 P.90 6-chloro-8- (difluoromethoxy)-N-methyl-N-[(1S)-1-(2- pyrimidin-2-yl-1,2,4- triazol-3-yl)ethyl]quinazolin-4- amine

0.83 433 3 P.91 8-chloro-6- (difluoromethoxy)-N- methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4- triazol-3- yl)ethyl]quinazolin-4- amine

0.83 433 3 P.92 N-[1-[2-(5- bromopyrimidin-2-yl)-1,2,4-triazol-3-yl]ethyl]- 6,8- bis(trifluoromethyl)quina- zolin-4-amine

1.07 533-535 (Br pattern) 3 P.93 6-chloro-8- (difluoromethoxy)-N-[(1S)-1-(2-pyrimidin-2- yl-1,2,4-triazol-3- yl)ethyl]quinazolin-4- amine

0.79 419-421 (Cl pattern) 3 P.94 8-chloro-6- (difluoromethoxy)-N-[(1S)-1-(2-pyrimidin-2- yl-1,2,4-triazol-3- yl)ethyl]quinazolin-4- amine

0.80 419-421 (Cl pattern) 3 P.95 8-iodo-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4- triazol-3-yl)ethyl]-6-(trifluoromethyl)quinazolin- 4-amine

0.96 513 3 174- 177 P.96 8-bromo-N-[1-(3- pyrimidin-2-ylpyrazin-2-yl)ethyl]-6- (trifluoromethyl)quinazolin- 4-amine

0.93 476-478 (Br pattern) 4 250- 252 P.97 8-bromo-N-methyl-N-[1-(3-pyrimidin-2-ylpyrazin- 2-yl)ethyl]-6- (trifluoromethyl)quinazolin-4-amine

1.03 490-492 (Br pattern) 4 110- 112 P.98 6-bromo-N-methyl-N-[1-(3-pyrimidin-2-ylpyrazin- 2-yl)ethyl]-8- (trifluoromethyl)quinazolin-4-amine

1.61 490-492 (Br pattern) 5 120- 122 P.99 8-bromo-N-(cyclopropylmethyl)-N- [1-(3-pyrimidin-2- ylpyrazin-2-yl)ethyl]-6-(trifluoromethyl)quinazolin- 4-amine

1.71 530-532 (Br pattern) 5 79-81 P.100 8-chloro-N-methyl-N-[1-(3-pyrimidin-2-ylpyrazin- 2-yl)ethyl]-6- (trifluoromethyl)quinazolin-4-amine

1.46 446 5 152- 154 P.101 8-chloro-N-[1-(3- pyrimidin-2-ylpyrazin-2-yl)ethyl]-6- (trifluoromethyl)quinazolin- 4-amine

1.47 432 5 240- 242 P.102 8-chloro-N-methyl-N-[1-[3-(triazol-2-yl)pyrazin- 2-yl]ethyl]-6- (trifluoromethyl)quinazolin-4-amine

1.59 435 5 164- 166 P.103 N-methyl-N-[1-[3- (triazol-2-yl)pyrazin-2-yl]ethyl]-6,8- bis(trifluoromethyl)quina- zolin-4-amine

1.16 470 4 134- 135 P.104 8-bromo-N-methyl-N-[1-[3-(triazol-2-yl)pyrazin- 2-yl]ethyl]-6- (trifluoromethyl)quinazolin-4-amine

1.10 479-481 (Br pattern) 4 164- 165 P.105 6-bromo-N-methyl-N-[1-[3-(triazol-2-yl)pyrazin- 2-yl]ethyl]-8- (trifluoromethyl)quinazolin-4-amine

1.15 479-481 (Br pattern) 4 175- 177 P.106 N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-6,8- bis(trifluromethyl)quina- zolin-4-amine

1.10 456 4 223- 225 P.107 N-methyl-N-[1-(3- pyrimidin-2-ylpyrazin-2-yl)ethyl]-6,8- bis(trifluoromethyl)quina- zolin-4-amine

1.66 480 5 139- 141 P.108 N-(cyclopropylmethyl)- N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-6,8- bis(trifluoromethyl)quina- zolin-4-amine

1.20 521 4 75-77 P.109 N-[1-[3-[5- (difluoromethoxy)-2-pyridyl]pyrazin-2- yl]ethyl]-6,8- bis(trifluoromethyl)quina-zolin-4-amine

1.21 532 4 141- 143 P.110 N-[1-[3-[5- (difluoromethoxy)-2-pyridyl]pyrazin-2- yl]ethyl]-N-methyl-6,8- bis(trifluoromethyl)quina-zolin-4-amine

1.21 546 4 212- 123 P.111 8-bromo-N-[1-[3-[5- (difluoromethoxy)-2-pyridyl]pyrazin-2- yl]ethyl]-6- (trifluoromethyl)quinazolin- 4-amine

1.15 543 4 147- 149 P.112 8-chloro-N-[1-[3-[5- (difluroomethoxy)-2-pyridyl]pyrazin-2- yl]ethyl]-N-methyl-6- (trifluoromethyl)quinazolin-4-amine

1.15 511 4 80-82 P.113 8-chloro-N-[1-[3-[5- (difluoromethoxy)-2-pyridyl]pyrazin-2- yl]ethyl]-6- (trifluoromethyl)quinazolin- 4-amine

1.12 498 4 109- 111 P.114 8-bromo-N-[1-[3-[5- (difluoromethoxy)-2-pyridyl]pyrazin-2- yl]ethyl]-N-methyl-6- (trifluoromethyl)quinazolin-4-amine

1.17 557 4 76-78 P.115 6-[3-[1-[[6,8- bis(trifluoromethyl)quina-zolin-4- yl]amino]ethyl]pyrazin-2- yl]pyridine-3-carbonitrile

1.15 491 4 248- 250 P.116 6-[3-[1-[[6,8- bis(trifluoromethyl)quina-zolin-4-yl]-methyl- amino]ethyl]pyrazin-2- yl]pyridine-3-carbonitrile

1.18 505 4 192- 194 P.117 6-[3-[1-[[8-bromo-6-(trifluoromethyl)quinazolin- 4- yl]amino]ethyl]pyrazin-2-yl]pyridine-3-carbonitrile

1.58 500-502 (Br pattern) 5 252- 254 P.118 6-[3-[1-[[6-chloro-8-(trifluoromethyl)quinazolin- 4- yl]amino]ethyl]pyrazin-2-yl]pyridine-3-carbonitrile

159 456 5 216- 218 P.119 6-[3-[1-[[6-bromo-8-(trifluoromethyl)quinazolin- 4- yl]amino]ethyl]pyrazin-2-yl]pyridine-3-carbonitrile

1.14 500-502 (Br pattern) 4 214- 216 P.120 6-chloro-N-[1-[3-[5-(difluoromethoxy)-2- pyridyl]pyrazin-2- yl]ethyl]-8-(trifluoromethyl)quinazolin- 4-amine

1.69 497 5 248- 250 P.121 6-[3-[1-[[8-chloro-6-(trifluoromethyl)quinazolin- 4- yl]amino]ethyl]pryazin-2-yl]pyridine-3-carbonitrile

1.53 456 5 249- 251 P.122 6-[3-[1-[[[8-chloro-6-(trifluoromethyl)quinazolin- 4-yl]-methyl- amino]ethyl]pyrazin-2-yl]pyridine-3-carbonitrile

1.55 470 5 201- 203 P.123 6-chloro-N-[1-[3-[5- (difluoromethoxy)-2-pyridyl]pyrazin-2- yl]ethyl]-N-methyl-8- (trifluoromethyl)quinazolin-4-amine

1.20 511 4 140- 142 P.124 6-[3-[1-[[8-bromo-6-(trifluoromethyl)quinazolin- 4-yl]-methyl- amino]ethyl]pyrazin-2-yl]pyridine-3-carbonitrile

1.67 514-516 (Br pattern) 5 186- 188 P.125 6-[3-[1-[[6-bromo-8-(trifluoromethyl)quinazolin- 4-yl]-methyl- amino]ethyl]pyrazin-2-yl]pyridine-3-carbonitrile

1.74 514-516 (Br pattern) 5 225- 227 P.126 6-[3-[1-[[6,8-bis(trifluoromethyl)quina- zolin-4-yl]- (cyclopropylmethyl)amino]ethyl]pyrazin-2- yl]pyridine-3-carbonitrile

1.31 545 4 165- 167 P.127 6-bromo-N-methyl-N-[1-(2-pyrimidin-2-yl-1,2,4- triazol-3-yl)ethyl]-8-(trifluoromethyl)quinazolin- 4-amine

1.53 479-481 (Br pattern) 5 200- 202 P.128 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin- 4-yl]-ethyl- amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbonitrile

75-77 P.129 6-chloro-N-methyl-N-[1- [3-(triazol-2-yl)pyrazin-2-yl]ethyl]-8- (trifluoromethyl)quinazolin- 4-amine

1.16 470 4 150- 152 P.130 6-chloro-N-[1-(3- pyrimidin-2-ylpyrazin-2-yl)ethyl]-8- (trifluoromethyl)quinazolin- 4-amine

1.04 446 4 226- 230 P.131 6-chloro-N- (cyclopropylmethyl)-N-[1-(3-pyrimidin-2- ylpyrazin-2-yl)ethyl]-8- (trifluoromethyl)quinazolin-4-amine

1.68 486 5 161- 163 P.132 6-chloro-N-methyl-N-[1-(3-pyrimidin-2-ylpyrazin- 2-yl)ethyl]-8- (trifluoromethyl)quinazolin-4-amine

1.04 446 4 144- 146 P.133 6-bromo-N-[1-(3- pyrimidin-2-ylpyrazin-2-yl)ethyl]-8- (trifluoromethyl)quinazolin- 4-amine

1.61 490-492 (Br pattern) 5 193- 195 P.134 6-[5-[(1R)-1-[[6,8-bis(trifluoromethyl)cinnolin- 4-yl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3- carboxamide

0.94 497 3 P.135 6-[5-[(1R)-1-[[6,8- bis(trifluoromethyl)cinnolin-4-yl]amino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile

1.01 480 3 P.136 N-[1-(2-pyrimidin-2-yl- 1,2,4-triazol-3-yl)ethyl]- 6,8-bis(trifluoromethyl)cinnolin- 4-amine

0.91 455 3 P.137 6-chloro-N-methyl-N- [(1S)-1-[2-[5-(1H-tetrazol-5-yl)-2-pyridyl]- 1,2,4-triazol-3-yl]ethyl]- 8-(trifluoromethyl)quinazolin- 4-amine

1.06 502.27 4 77-79 P.138 4-[[(1S)-1-(2-pyrimidin- 2-yl-1,2,4-triazol-3-yl)ethyl]amino]-6,8- bis(trifluoromethyl)quino- line-3-carbonitrile

1.10 479.63 4 203- 205 P.139 4-[[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3- yl]ethyl]amino]-6,8-bis(trifluoromethyl)quino- line-3-carbonitrile

1.18 503.21 4 204- 206 P.140 4-[methyl-[(1S)-1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]amino]- 6,8- bis(trifluoromethyl)quino-line-3-carbonitrile

1.13 493.63 4 84-86 P.141 4-[[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3- yl]ethyl]-methyl-amino]- 6,8-bis(trifluoromethyl)quino- line-3-carbonitrile

1.19 517.26 4 88-90 P.142 6-chloro-N-methyl-8-(trifluoromethyl)-N-[(1S)- 1-[2-[5-[4- (trifluoromethyl)thiazol-2-yl]-2-pyridyl]-1,2,4- triazol-3- yl]ethyl]quinazolin-4- amine

1.26 535.24 4 84-86 P.143 6-chloro-N-methyl-N- [(1S)-1-[2-(5-thiazol-2-yl-2-pyridyl)-1,2,4- triazol-3-yl]ethyl]-8- (trifluoromethyl)quinazolin-4-amine

1.19 517.25 4 142- 144 P.144 6-bromo-8-chloro-N- methyl-N-[1-(3-pyrimidin-2-ylpyrazin-2- yl)ethyl]quinazolin-4- amine

0.90 456 3 P.145 N-[(1S)-1-(2-pyrimidin- 2-yl-1,2,4-triazol-3-yl)ethyl]-6,8- bis(trifluoromethyl)- 1,2,3-benzotriazin-4- amine

0.92 456 3 P.146 6-cyclopropyl-N-methyl- N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethyl]-8- (trifluroomethyl)quinazolin- 4-amine

0.97 441 3 182- 184 P.147 8-cyclopropyl-N-methyl-N-[(1S)-1-(2-pyrimidin- 2-yl-1,2,4-triazol-3- yl)ethyl]-6-(trifluoromethyl)quinazolin- 4-amine

0.89 441 3 P.148 6-[3-[(1S)-1-[[6-iodo-8- (trifluoromethyl)quinazolin-4-yl]-methyl- amino]ethyl]pyrazin-2- yl]pyridine-3-carbonitrile

1.15 562 3 P.149 6-[3-[(1S)-1-[[8-iodo-6- (trifluoromethyl)quinazolin-4-yl]-methyl- amino]ethyl]pyrazin-2- yl]pyridine-3-carbonitrile

1.15 562 3 P.150 6-chloro-N-methyl-N- [(1S)-1-[2-[5-(1,2,4-oxadiazol-3-yl)-2- pyridyl]-1,2,4-triazol-3- yl]ethyl]-8-(trifluoromethyl)quinazolin- 4-amine

1.16 502.39 4 144- 146 P.151 6-chloro-N-methyl-8-(trifluoromethyl)-N-[(1S)- 1-[2-[5-[5- (trifluoromethyl)-1,2,4-oxadiazol-3-yl]-2- pyridyl]-1,2,4-triazol-3- yl]ethyl]quinazolin-4-amine

1.27 570.25 4 75-77 P.152 8-chloro-N-[1-[2-[5- (difluoromethoxy)-2-pyridyl]-1,2,4-triazol-3- yl]ethyl]-6- (trifluoromethyl)quinazolin-4-amine

1.52 486.1 5 240- 242 P.153 8-chloro-N-[1-[2-[5- (difluoromethoxy)-2-pyridyl]-1,2,4-triazol-3- yl]ethyl]-N-methyl-6-(trifluoromethyl)quinazolin- 4-amine

1.53 500.2 5 102- 104 P.154 8-bromo-N-[1-[2-[5- (difluoromethoxy)-2-pyridyl]-1,2,4-triazol-3- yl]ethyl]-N-methyl-6-(trifluoromethyl)quinazolin- 4-amine

1.55 546.1 5 75-77 P.155 6-[5-[(1S)-1-[[6,8- bis(trifluoromethyl)quina-zolin-4-yl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3-carboxamide

1.05 511.66 4 183- 185 P.156 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin- 4-yl]-methyl- amino]ethyl]-1,2,4-triazol-1-yl]-N′-hydroxy- pyridine-3- carboxamidine

1.01 492.26 4 223- 225 P.157 6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quina- zolin-4-yl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3- carboxamide

1.03 497.27 4 P.158 6-[5-[1-[(8-bromo-6- chloro-quinazolin-4-yl)amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3- carbonitrile

0.98 455 3 P.159 6-bromo-8-chloro-N-[1- (2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethyl]quinazolin-4- amine

0.81 431 3 P.161 6-[3-[(1S)-1-[[8-iodo-6- (trifluoromethyl)quinazolin-4- yl]amino]ethyl]pyrazin-2- yl]pyridine-3-carbonitrile

1.12 548 3 153- 155 P.162 6-[3-[(1S)-1-[[6-iodo-8-(trifluoromethyl)quinazolin- 4- yl]amino]ethyl]pyrazin-2-yl]pyridine-3-carbonitrile

1.12 548 3 205- 208 P.163 6-[5-[(1S)-1-[[6- [cyclopropyl(difluoro)meth-yl]-8- (trifluoromethyl)quinazolin- 4-yl]-methyl- amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbonitrile

1.12 515 3 P.164 N-[(1S)-1-[2-(5- bromopyrimidin-2-yl)-1,2,4-triazol-3-yl]ethyl]- N-methyl-6,8- bis(trifluoromethyl)quina-zolin-4-amine

1.11 547-549 (Br pattern) 3 P.165 6,8-dichloro-7-fluoro-N-methyl-N-[1-(2- pyrimidin-2-yl-1,2,4- triazol-3- yl)ethyl]quinazolin-4-amine

0.91 419 3 145- 225 P.166 6,8-dichloro-7-fluoro-N- [1-(2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethyl]quinazolin-4- amine

0.86 405 3 215- 155 P.167 methyl N-[6,8- bis(trifluoromethyl)quina-zolin-4-yl]-N-[1-[2-(5- cyano-2-pyridyl)-1,2,4- triazol-3-yl]ethyl]carbamate

1.08 537 3 P.168 6-[5-[(1S)-1-[[6,8- bis(trifluoromethyl)quina-zolin-4-yl]-ethyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3-carbonitrile

1.15 507 3 P.169 6-[5-[(1S)-1-[[6,8- bis(trifluoromethyl)quina-zolin-4-yl]- (methoxymethyl)amino] ethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile

1.14 523 3 P.170 6-[5-[(1S)-1-[[6- (cyclopropanecarbonyl)- 8-(trifluoromethyl)quinazolin- 4-yl]-methyl- amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbonitrile

1.06 493 3 P.171 8-bromo-6-chloro-N-[1- (2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethyl]quinazolin-4- amine

0.84 431 3 205- 238 P.172 8-bromo-6-chloro-N- methyl-N-[1-(2-pyrimidin-2-yl-1,2,4- triazol-3- yl)ethyl]quinazolin-4- amine

0.89 445 3 P.173 8-bromo-6-chloro-N-[1- [3-(triazol-2-yl)pyrazin-2-yl]ethyl]quinazolin-4- amine

0.93 431 3 175- 200 P.174 8-bromo-6-chloro-N- methyl-N-[1-[3-(triazol-2-yl)pyrazin-2- yl]ethyl]quinazolin-4- amine

1.00 445 3 105- 166 P.175 6-[3-[(1S)-1-[[6,8- bis(trifluoromethyl)quina-zolin-4-yl]-methyl- amino]ethyl]-5-methyl- pyraizn-2-yl]pyridine-3-carbonitrile

1.22 518 3 P.176 3-fluoro-N-methyl-N- [(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethyl]-6,8- bis(trifluoromethyl)quino-lin-4-amine

1.10 486 3 P.177 6-[5-[(1S)-1-[[6- cyclopropyl-8-(trifluoromethyl)quinazolin- 4-yl]-methyl- amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbonitrile

1.09 465 3 P.178 6-bromo-8-chloro-N-[1- (3-pyrimidin-2-ylpyrazin-2-yl)ethyl]quinazolin-4- amine

0.83 442 3 P.179 8-bromo-N-methyl-N-[1- [3-(triazol-2-yl)pyrazin-2-yl]ethyl]-6- (trifluoromethoxy)quinazo- lin-4-amine

1.07 495 3 P.180 6-bromo-8- (difluoromethoxy)-N-methyl-N-[1-[3-(triazol- 2-yl)pyrazin-2- yl]ethyl]quinazolin-4- amine

0.93 477 3 P.181 3-chloro-N-methyl-N- [(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethyl]-6,8- bis(trifluoromethyl)quino-lin-4-amine

1.14 502 3 P.182 8-bromo-6-chloro-N- methyl-N-[1-(3-pyrimidin-2-ylpyrazin-2- yl)ethyl]quinazolin-4- amine

0.90 456 3 P.183 8-bromo-6-chloro-N-[1- (3-pyrimidin-2-ylpyrazin-2-yl)ethyl]quinazolin-4- amine

0.84 424 3 P.184 6-[5-[(1S)-1-[[6-iodo-8- (trifluoromethyl)quinazolin-4-yl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3- carbonitrile

1.10 551 3 100- 102 P.185 8-bromo-N-[1-[2-(5- fluoro-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-N- methyl-6- (trifluoromethyl)quinazolin- 4-amine

1.55 495.9 (Br pattern) 5 159- 161 P.186 8-bromo-N-[1-[2-(5-fluoro-2-pyridyl)-1,2,4- triazol-3-yl]ethyl]-6-(trifluoromethyl)quinazolin- 4-amine

1.51 483.9 (Br pattern) 5 270- 272 P.187 6-chloro-N-[1-[2-(5-fluoro-2-pyridyl)-1,2,4- triazol-3-yl]ethyl]-N- methyl-8-(trifluoromethyl)quinazolin- 4-amine

1.57 452.3 5 140- 142 P.188 6-bromo-N-[1-[2-(5- fluoro-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-N- methyl-8- (trifluoromethyl)quinazolin- 4-amine

1.59 496.3 (Br pattern) 5 144- 146 P.189 N-[1-[2-(5-fluoro-2-pyridyl)-1,2,4-triazol-3- yl]ethyl]-N-methyl-6,8-bis(trifluoromethyl)quina- zolin-4-amine

130- 132 P.190 6-[5-[(1S)-1-[[6,8- bis(trifluoromethyl)quina-zolin-4-yl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3-carbothioamide

1.12 528.04 4 186- 188 P.191 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin- 4-yl]-methyl- amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbothioamide

1.10 493.24 4 169- 171 P.192 N-[2-[2-[5- (difluoromethoxy)-2-pyridyl]-1,2,4-triazol-3- yl]ethyl]-N-methyl-6,8-bis(trifluoromethyl)quina- zolin-4-amine

1.61 534.1 5 124- 126 P.193 N-[1-[2-[5- (difluoromethoxy)-2-pyridyl]-1,2,4-triazol-3- yl]ethyl]-6,8- bis(trifluoromethyl)quina-zolin-4-amine

1.59 520 5 226- 228 P.194 6-bromo-N-[1-[2-[5- (difluoromethoxy)-2-pyridyl]-1,2,4-triazol-3- yl]ethyl]-N-methyl-8-(trifluoromethyl)quinazolin- 4-amine

1.19 545.74 4 138- 140 P.195 6-bromo-N-[1-[2-[5- (difluoromethoxy)-2-pyridyl]-1,2,4-triazol-3- yl]ethyl]-8- (trifluoromethyl)quinazolin-4-amine

1.59 430.0 5 247- 249 P.196 6-bromo-N-[1-[3-(5- bromo-2-pyridyl)pyrazin-2-yl]ethyl]-N-methyl-8- (trifluoromethyl)quinazolin- 4-amine

1.29 569.24 4 166- 168 P.197 N-[1-[3-(5-bromo-2- pyridyl)pyrazin-2-yl]ethyl]-8-chloro-N- methyl-6- (trifluoromethyl)quinazolin- 4-amine

1.24 523.14 4 142- 144 P.198 6-bromo-N-[1-[3-(5-bromo-2-pyridyl)pyrazin- 2-yl]ethyl]-8- (trifluoromethyl)quinazolin-4-amine

1.28 553.04 4 232- 234 P.199 N-[1-[3-(5-bromo-2- pyridyl)pyrazin-2-yl]ethyl]-8-chloro-6- (trifluoromethyl)quinazolin- 4-amine

1.23 509.13 4 230- 232 P.200 6-[3-[1-[[6-chloro-8-(trifluoromethyl)quinazolin- 4-yl]- (cyclopropylmethyl)amino]ethyl]pyrazin-2- yl]pyridine-3-carbonitrile

1.28 510.36 4 254- 256 P.201 8- [cyclopropyl(difluoro)meth-yl]-N-methyl-N-[(1S)- 1-(2-pyrimidin-2-yl- 1,2,4-triazol-3-yl)ethyl]- 6-(trifluoromethyl)quinazolin- 4-amine

1.09 491 3 P.202 N-methyl-N-[(1S)-1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6- (trifluoromethyl)-8- (trifluoromethylsulfonyl)quinazolin-4-amine

1.04 433 3 P.203 6-[5-[(1R)-1-[[6-bromo- 8- (trifluoromethyl)quinazolin-4-yl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3- carbonitrile

1.09 503 (Br pattern) 3 P.204 6-[5-[(1S)-1-[[6-bromo- 8-(trifluoromethyl)quinazolin- 4-yl]-methyl- amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbonitrile

1.09 503 (Br pattern) 3 P.205 N-[1-(5-bromo-2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6- chloro-N-methyl-8- (trifluoromethyl)quinazolin-4-amine

1.05 513 3 149- 151 P.206 6-[5-[(1S)-1-[[6-bromo- 8-(trifluoromethyl)-4-quinolyl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3-carbonitrile

1.09 502 3 P.207 N-[1-(5-bromo-2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-8- chloro-N-methyl-6- (trifluoromethyl)quinazolin-4-amine

1.10 513 3 239- 242 P.208 6-bromo-N-methyl-N- [(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethyl]-8- (trifluoromethyl)quinazolin- 4-amine

0.99 478-4.80 (Br pattern) 3 P.209 8-bromo-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4- triazol-3-yl)ethyl]-6- (trifluoromethyl)quinolin-4-amine

0.68 464-466 (Br pattern) 3 247- 250 P.210 6-[5-[1-[[5,7-bis(trifluoromethyl)-1- isoquinolyl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3-carbonitrile

1.18 478 3 P.211 6-[5-[1-[[5,7- bis(trifluoromethyl)-1-isoquinolyl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3carbonitrile

1.21 492 3 P.212 3-bromo-N-methyl-N- [(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethyl]-6,8- bis(trifluoromethyl)quino-lin-4-amine

1.15 546-548 (Br pattern) 3 P.213 6-[5-[(1S)-1-[[8-[cyclopropyl(difluoro)meth- yl]-6- (trifluoromethyl)quinazolin-4-yl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3- carbonitrile

1.18 515 3 90-92 P.214 6-[5-[(1S)-1-[[6,8- bis(trifluoromethyl)-4-quinolyl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3-carbonitrile

1.13 492 3 P.215 6-[5-[(1S)-1-[methyl-[6- (trifluoromethyl)-8-(trifluoromethylsulfanyl) quinazolin-4- yl]amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbonitrile

1.19 525 3 75-78 P.216 6-[5-[1-[[6-bromo-8- (trifluoromethoxy)quinazo-lin-4-yl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3-carbonitrile

1.06 519 3 149- 150 P.217 6-[5-[1-[[8-bromo-6-(trifluoromethoxy)quinazo- lin-4-yl]-methyl- amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbonitrile

1.07 519 3 70-73 P.218 6-[5-[(1S)-1-[[6-iodo-8-(trifluoromethyl)quinazolin- 4-yl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3-carbonitirle

1.08 537 3 264- 266 P.219 8-iodo-N-methyl-N- [(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethyl]-6- (trifluoromethyl)quinazolin- 4-amine

1.01 427 3 135- 137 P.220 6-[5-[1-[[6- (trifluoromethoxy)-8-(trifluoromethyl)quinazolin- 4-yl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3-carbonitrile

1.08 495 3 145- 157 P.221 6-[5-[1-[methyl-[6- (trifluoromethoxy)-8-(trifluoromethyl)quinazolin- 4-yl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3-carbonitrile

1.11 509 3 P.222 6-[5-[1-[(6,8-dichloro-7- fluoro-quinazolin-4-yl)amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3- carbonitrile

0.98 429 3 215- 225 P.223 6-[5-[1-[(6,8-dichloro-7-fluoro-quinazolin-4-yl)- methyl-amino)ethyl]- 1,2,4-triazol-1-yl]pyridine-3-carbonitrile

1.01 443 3 145- 155 P.224 4-[1-[2-(5-cyano-2- pyridyl)-1,2,4-tirazol-3-yl]ethyl-methyl-amino]- 6,8- bis(trifluoromethy)quino-line-3-carbonitrile

1.61 515.0 5 174- 176 P.225 N-[(4- methoxyphenyl)methyl]-N-[1-(3-pyrimidin-2- ylpyrazin-2-yl)ethyl]-6,8-bis(trifluoromethyl)quina- zolin-4-amine

1.21 586.71 4 112- 114 P.226 phenyl N-[6,8- bis(trifluoromethyl)quina-zolin-4-yl]-N-[(1S)-1-[2- (5-cyano-2-pyridyl)- 1,2,4-triazol-3-yl]ethyl]carbamate

1.21 599.74 4 95-97 P.227 6-[5-[(1S)-1-[[8- (cyclopropanecarbonyl)- 6-(trifluoromethyl)quinazolin- 4-yl]-methyl- amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbonitrile

0.97 493 3 P.228 6-[5-[(1S)-1-[[8-iodo-6- (trifluoromethyl)quinazolin-4-yl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3- carbonitrile

1.12 551 3 86-90 P.229 8-bromo-N-[1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6- (trifluoromethoxy)quinazo- line-4-amine

0.91 481 3 P.230 6-[5-[1-[[6-bromo-8- (difluoromethoxy)quinazo-lin-4-yl]-methyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3-carbonitrile

0.96 501-503 (Br pattern) 3 P.231 6-bromo-N-[1-[2-(5-fluoro-2-pyridyl)-1,2,4- triazol-3-yl]ethyl]-8-(trifluoromethyl)quinazolin- 4-amine

1.57 481.9 (Br pattern) 5 282- 284 P.232 8-chloro-N-[1-[2-(5-fluoro-2-pyridyl)-1,2,4- triazol-3-yl]ethyl]-N- methyl-6-(trifluoromethyl)quinazolin- 4-amine

1.52 452.0 5 184- 186 P.233 N-[1-[2-(5-fluoro-2-pyridyl)-1,2,4-triazol-3- yl]ethyl]-6,8- bis(trifluoromethyl)quina-zolin-4-amine

1.59 472.0 5 274- 276 P.234 6-chloro-N-[1-[2-(5-fluroo-2-pyridyl)-1,2,4- triazol-3-yl]ethyl]-8-(trifluoromethyl)quinazolin- 4-amine

1.56 438.0 5 262- 264 P.235 6-chloro-N-[1-[2-[5- (difluoromethoxy)-2-pyridyl]-1,2,4-triazol-3- yl]ethyl]-8- (trifluoromethyl)quinazolin-4-amine

1.12 486.31 4 236- 238 P.236 6-chloro-N-[1-[2-[5- (difluoromethoxy)-2-pyridyl]-1,2,4-triazol-3- yl]ethyl]-N-methyl-8-(trifluoromethyl)quinazolin- 4-amine

1.59 500 5 131- 133 P.237 6-bromo-N-[1-[2-(5- bromo-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-N- methyl-8- (trifluoromethyl)quinazolin- 4-amine

1.65 557.8 (Di- bromo pattern) 5 119- 121 P.238 N-[1-[2-(5-bromo-2-pyridyl)-1,2,4-triazol-3- yl]ethyl]-6-chloro-N- methyl-8-(trifluoromethyl)quinazolin- 4-amine

1.65 513.9 (Br + Cl pattern) 5 122- 124 P.239 8-bromo-N-[1-[2-(5-bromo-2-pyridyl)-1,2,4- triazol-3-yl]ethyl]-N- methyl-6-(trifluoromethyl)quinazolin- 4-amine

1.63 557.8 (Di- bromo pattern) 5 123- 125 P.240 N-[1-[2-(5-bromo-2-pyridyl)-1,2,4-triazol-3- yl]ethyl]-8-chloro-N- methyl-6-(trifluoromethyl)quinazolin- 4-amine

1.59 513.9 (Br, Cl pattern) 5 130- 132 P.241 N-[1-[2-(5-bromo-2-pyridyl)-1,2,4-triazol-3- yl]ethyl]-N-methyl-6,8-bis(trifluoromethyl)quina- zolin-4-amine

1.67 547.9 (Br pattern) 5 157- 159 P.242 4-[1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3- yl]ethylamino]-6,8- bis(trifluoromethyl)quino-ine-3-carbonitrile

1.18 503.64 4 261- 263 P.243 6-bromo-8- (difluoromethoxy)-N-[1-(2-pyrimidin-2-yl-1,2,4- triazol-3- yl)ethyl]quinazolin-4- amine

0.80 363-465 (Br pattern) 3 220- 223 P.244 6-[5-[1-[[6-bromo-8-(difluoromethoxy)quinazo- lin-4-yl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3-carbonitrile

0.93 487-489 (Br pattern) 3 P.245 6-bromo-8- (difluoromethoxy)-N-methyl-N-[1-(2- pyrimidin-2-yl-1,2,4- triazol-3- yl)ethyl]quinazolin-4-amine

0.84 477-479 (Br pattern) 3 P.246 6-[5-[1-[[8-bromo-6-(trifluoromethoxy)quinazo- lin-4-yl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3-carbonitrile

1.02 505-507 (Br patterns) 3 P.247 6-[5-[1-[[6-bromo-8-(trifluoromethoxy)quinazo- lin-4-yl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3-carbonitrile

1.03 505-507 (Br pattern) 3 P.248 6-bromo-N-[1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-8- (trifluoromethoxy)quina- zolin-4-amine

0.91 481-483 (Br pattern) 3 133- 135 P.249 N-methyl-N-[1-(3-pyrimidin-2-ylpyrazin-2- yl)ethyl]-6,8- bis(trifluoromethyl)quino-lin-4-amine

1.08 479 3 P.250 N-methyl-N-[1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-5,7- bis(trifluoromethyl)isoquino- lin-1-amine

1.12 468 3 P.251 6-[5-[(1S)-1-[[6,8- bis(trifluoromethyl)-4-quinolyl]amino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile

1.02 478 3 P.252 6-[5-[(1S)-1-[[6-bromo- 8-(trifluoromethyl)-4-quinolyl]amino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile

0.89 488-490 (Br pattern) 3 P.253 6-bromo-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4- triazol-3-yl)ethyl]-8- (trifluoromethyl)quinolin-4-amine

0.76 464-466 (Br pattern) 3 245- 250 P.254 6-[5-[(1S)-1-[[8-bromo-6-(trifluoromethyl)-4- quinolyl]-methyl- amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbonitrile

098 502-504 (Br pattern) 3 170- 172 P.255 8-bromo-N-methyl-N-[(1S)-1-(2-pyrimidn-2- yl-1,2,4-triazol-3- yl)ethyl]-6-(trifluoromethyl)quinolin- 4-amine

0.88 478-480 (Br pattern) 3 162- 165 P.256 6-[5-[(1S)-1-[[8-bromo-6-(trifluoromethyl)-4- quinolyl]amino]ethyl]- 1,2,4-triazol-1-yl]pyridine-3-carbonitrile

0.78 488-490 (Br pattern) 3 262- 265 P.257 6-[5-[1-[(6,8-dibromoquinazolin-4-yl)- methyl-amino]ethyl]- 1,2,4-triazol-1-yl]pyridin-3-carbonitrile

1.02 513 3 155- 159 P.258 6,8-dibromo-N-methyl- N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethyl]quinazolin-4- amine

0.90 489 3 135- 142 P.259 N-[6,8- bis(trifluoromethyl)quina-zolin-4-yl]-N-[1-[2-(5- cyano-2-pyridyl)-1,2,4- triazol-3-yl]ethyl]acetamide

1.03 521 3 P.260 6-[5-[1-[allyl-[6,8- bis(trifluoromethyl)quina-zolin-4-yl]amino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile

1.18 519 3 P.261 6-[5-[1-[[6,8- bis(trifluoromethyl)quina-zolin-4-yl]-prop-2-ynyl- amino]ethyl]-1,2,4- triazol-1-yl]pyridine-3-carbonitrile

1.10 517 3 P.262 N-methyl-N-[(1S)-1-(2- pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-8- (trifluoromethyl)-6- (trifluoromethylsulfonyl)quinazolin-4-amine

1.04 533 3 P.263 6-[5-[(1S)-1-[[8-iodo-6- (trifluoromethyl)quinazolin-4-yl]amino]ethyl]- 1,2,4-triazol-1- yl]pyridine-3-carbonitrile

1.08 537 3 236- 238 P.264 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin- 4-yl]- (cyclopropylmethyl)amino]ethyl]-1,2,4-triazol-1- yl]pyridine-3-carbonitrile

1.25 499.26 4 75-77 P.265 6-chloro-N- (cyclopropylmethyl)-N-[(1S)-1-(2-pyrimidin-2- yl-1,2,4-triazol-3- yl)ethyl]-8-(trifluoromethyl)quinazolin- 4-amine

1.17 475.29 4 110- 112 P.266 6-[5-[1-[[8-bromo-6-(trifluoromethyl)quinazolin- 4-yl]-methyl- amino]ethyl]-1,2,4-triazol-1-yl]pyridine-3- carbonitrile

1.10 503.13 4 165- 167 P.267 N-[1-[2-(5-bromo-2-pyridyl)-1,2,4-triazol-3- yl]ethyl]-8-chloro-6-(trifluoromethyl)quinazolin- 4-amine

1.59 497.8 (Cl pattern) 5 273- 275 P.268 N-[1-[2-(5-bromo-2-pyridyl)-1,2,4-triazol-3- yl]ethyl]-6,8- bis(trifluoromethyl)quina-zolin-4-amine

1.21 532.11 4 274- 276 P.269 8-bromo-N-[1-[2-(5- bromo-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-6- (trifluoromethyl)quinazolin- 4-amine

1.17 542.07 (Di- bromo pattern) 4 280- 282 P.270 N-[1-[2-(5-bromo-2-pyridyl)-1,2,4-triazol-3- yl]ethyl]-6-chloro-8-(trifluoromethyl)quinazolin- 4-amine

1.61 5 274- 276 P.271 6-[5-[(1S)-1-[[8-chloro-6-(trifluoromethyl)quinazolin- 4-yl]- (cyclopropylmethyl)amino]ethyl]-1,2,4-triazol-1- yl]pyridine-3-carbonitrile

1.18 499.27 4 128- 130 P.272 8-chloro-N- (cyclopropylmethyl)-N-[(1S)-1-(2-pyrimidin-2- yl-1,2,4-triazol-3- yl)ethyl]-6-(trifluoromethyl)quinazolin- 4-amine

1.50 475.0 5 72-74 P.273 6-bromo-N-[1-[3-[5- (difluoromethoxy)-2-pyridyl]pyrazin-2- yl]ethyl]-N-methyl-8- (trifluoromethyl)quinazolin-4-amine

1.21 554.74 4 120- 122 P.274 8-chloro-N-[1-[2-(5-fluroo-2-pyridyl)-1,2,4- triazol-3-yl]ethyl]-6-(trifluoromethyl)quinazolin- 4-amine

1.51 437.9 5 P.275 6-[3-[1-[[6-chloro-8- (trifluoromethyl)quinazolin-4-yl]-methyl- amino]ethyl]pyrazin-2- yl]pyridine-3-carbonitrile

1.20 470.21 4 217- 219 P.276 6- [cyclopropyl(difluoro)meth-yl]-N-methyl-N-[(1S)- 1-(2-pyrimidin-2-yl- 1,2,4-triazol-3-yl)ethyl]- 8-(trifluromethyl)quinazolin- 4-amine

1.05 491 3 P.277 8-chloro-N-[1-[3-(triazol- 2-yl)pyrazin-2-yl]ethyl]pyrido[3,4- d]pyrimidin-4-amine

0.72 354 3

Table for Compounds of formula III(i):

RT [M + H] Entry IUPAC name STRUCTURE (min) (measured) Method NMRIII(i).1 6-[5-(1-aminoethyl)-3- bromo-1,2,4-triazol-1-yl]pyridine-3-carbonitrile

0.65 293, 295 1 III(i).2 1-[5-bromo-2-[5-(2,2-difluoroethoxy)pyrimidin-2- yl]-1,2,4-triazol-3- yl]ethanamine

0.37 349, 351 1 III(i).3 1-[2-[5-(2,2- difluoroethoxy)pyrimidin-2-yl]-1,2,4-triazol-3- yl]ethanamine

1 III(i).4 6-[5-(1-aminoethyl)-1,2,4- triazol-1-yl]pyridine-3-carbonitrile

0.22 215 1 III(i).5 1-[2-[5- (difluoromethoxy)pyrimidin-2-yl]-1,2,4-triazol-3- yl]ethanamine

2 III(i).6 1-[5-bromo-2-[5-(2,2,2- trifluoroethoxy)pyrimidin-2-yl]-1,2,4-triazol-3- yl]ethanamine

III(i).7 1-[2-(5-fluoro-2-pyridyl)- 1,2,4-triazol-3- yl]ethanamine

0.24 208 1 III(i).8 1-[5-bromo-2-(5-fluoro-2- pyridyl)-1,2,4-triazol-3-yl]ethanamine

3 III(i).9 1-(5-bromo-2-pyrimidin-2- yl-1,2,4-triazol-3- yl)ethanamine

0.52 269, 271 1 III(i).10 1-(5-methoxy-2-pyrimidin-2-yl-1,2,4-triazol-3- yl)ethanamine

0.18 221 1 III(i).11 5-(1-aminoethyl)-1- pyrimidin-2-yl-1,2,4-triazole-3-carbonitrile

0.56 216 1 III(i).12 1-[5-(2-methoxyethoxy)-2- pyrimidin-2-yl-1,2,4-3-yl]ethanamine

0.19 265 1 III(i).13 1-(5-chloro-2-pyrimidin-2- yl-1,2,4-triazol-3-yl)ethanamine)

0.20 225, 227 1 III(i).14 1-(5-methylsulfonyl-2-pyrimidin-2-yl-1,2,4-triazol- 3-yl)ethanamine)

0.31 269 1 III(i).15 1-[3-(5-fluoro-2- pyridyl)pyrazin-2-3-yl)ethanamine

0.32 219 1 III(i).16 1-(3-pyrimidin-2-ylpyrazin- 2-yl)ethanamine

0.40 202 1 III(i).17 1-[3-(2-pyridyl)pyrazin-2- yl]ethanamine

III(i).18 1-[3-(5- cyclopropylpyrimidin-2- yl)pyrazin-2-yl]ethanamine

III(i).19 1-[3-[5-(2,2- difluoroethoxy)pyrimidin-2-yl]pyrazin-2-yl]ethanamine

III(i).20 1-[3-(5-bromo-2- pyridyl)pyrazin-2- yl]ethanamine

III(i).21 6-[3-(1-aminoethyl)pyrazin- 2-yl]pyridine-3-carbonitrile

III(i).22 1-[3-(triazol-2-yl)pyrazin-2- yl]ethanamine

0.18 191 1

RT [M + H] Entry IUPAC name STRUCTURE (min (measured) Method V(i).12-(1-bromoethyl)-3- pyrimidin-2-yl-pyrazine

0.65 265, 267 1 V(i).2 2-[5-(1-bromoethyl)-1,2,4- triazol-1-yl]pyridine

0.82 253, 255 1 V(i).3 2-[5-(1-bromoethyl)-1,2,4-triazol-1-yl]pyrimidine

0.63 254, 256 1 V(i).4 2-[3-bromo-5-(1- bromoethyl)-1,2,4-triazol-1-yl]pyrimidine

0.85 332, 334, 336 1 V(i).5 2-[3-bromo-5-(1-bromoethyl)-1,2,4-triazol-1- yl]-5-(2,2,2- trifluoroethoxy)pyrimidine

V(i).6 6-[5-(1-bromoethyl)-1,2,4- triazol-1-yl]pyridine-3- carbonitrile

0.88 278, 280 1 V(i).7 6-[3-bromo-5-(1- bromoethyl)-1,2,4-triazol-1-yl]pyridine-3-carbonitrile

1.01 356, 358, 360 1 V(i).8 2-[5-(1-bromoethyl)-1,2,4- triazol-1-yl]-5-(difluoromethoxy)pyrimidine

0.82 320, 322 1 V(i).9 2-[3-bromo-5-(1- bromoethyl)-1,2,4-triazol-1-yl]-5- (difluoromethoxy)pyridine

V(i).10 2-[5-(1-bromoethyl)-1,2,4- triazol-1-yl]-5-(2,2- difluoroethoxy)pyrimidine

0.82 334, 336 1 V(i).11 5-(1-bromoethyl)-1-[4-(trifluoromethoxy)phenyl]- 1,2,4-triazole

1.04 336, 338 1 V(i).12 5-(1-chloroethyl)-1-[4-(trifluoromethoxy)phenyl]- 1,2,4-triazole

1.02 292 1 V(i)-13 2-[3-bromo-5-(1- bromoethyl)-1,2,4-triazol-1-yl]-5-(2,2- difluoroethoxy)pyrimidine

0.96 412, 414, 416 1 V(i).14 2-[5-(1-bromoethyl)-3-methoxy-1,2,4-triazol-1- yl]pyrimidine

0.75 284, 286 1 V(i).15 2-[5-(1-bromoethyl)-1,2,4-triazol-1-yl]-5-fluoro- pyridine

0.88 271, 273 1 V(i).16 5-(1-bromoethyl)-1- pyrimidin-2-yl-1,2,4-triazole-3-carbonitrile

0.85 279, 281 1 V(i).17 2-[5-(1-bromoethyl)-3- chloro-1,2,4-triazol-1-yl]pyrimidine

0.84 288, 290, 292 1 V(i).18 2-[5-(1-bromoethyl)-3-(2-methoxyethoxy)-1,2,4- triazol-1-yl]pyrimidine

0.78 328, 330 1 V(i).19 4-[3-bromo-5-(1- bromoethyl)-1,2,4-triazol-1-yl]-2-fluoro-pyridine

0.97 349, 351, 353 1 V(i).20 2-[3-bromo-5-(1-bromoethyl)-1,2,4-triazol-1- yl]-5-fluoro-pyridine

1.07 349, 351, 353 1 V(i).21 6-[5-(1-bromoethyl)-3-cyano-1,2,4-triazol-1- yl]pyridine-3-carbonitrile

1.00 303, 305 1 V(i).22 5-bromo-2-[5-(1- bromoethyl)-1,2,4-triazol-1-yl]pyrimidine

Table for Compounds of formula VII(i):

RT [M + H] Entry IUPAC name STRUCTURE (min) (measured) Method VII(i).11-[2-(2-pyridyl)-1,2,4- triazol-3-yl]ethanone

0.50 189 1 VII(i).2 1-(3-pyrimidin-2-ylpyrazin- 2-yl)ethanone

0.41 201 1 VII(i).3 1-[3-(5-fluoro-2- pyridyl)pyrazin-2- yl]ethanone

0.77 218 1 VII(i).4 1-[3-(2-pyridyl)pyrazin-2- yl]ethanone

0.35 200 1 VII(i).5 1-[3-(5- cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethanone

VII(i).6 6-(3-acetylpyrazin-2- yl)pyridine-3-carbonitrile

0.73 225 1 VII(i).7 1-[3-[5-(2,2,2- trifluoroethoxy)-2-pyridyl]pyrazin-2- yl]ethanone

VII(i).8 1-[3-[5- (difluoro methoxy) pyrimidin-2-yl]pyrazin-2-yl]ethanone

VII(i).9 1-[3-(5-chloro-2- pyridyl)pyrazin-2- yl]ethanone

VII(i).10 1-[3-(5-bromo-2- pyridyl)pyrazin-2- yl]ethanone

VII(i).11 1-[3-(triazol-2-yl)pyrazin-2- yl]ethanone

0.53 190 1

-   -   1. 1H NMR (400 MHz, DMSO) δ ppm 1.57 (d, J=6.97 Hz, 3H) 4.65        (td, J=14.67, 3.30 Hz, 2H) 5.10 (q, J=6.85 Hz, 1H) 6.34-6.67 (m,        1H) 7.47 (br s, 2H) 8.30 (s, 1H) 8.85 (s, 2H);    -   2. 1 H NMR (400 MHz, DMSO d6) δ ppm 1.57-1.62 (d, 3H) 5.02-5.33        (q, 1H) 7.28-7.72 (t, 1H) 7.73-7.99 (s, 2H) 8.25-8.44 (s, 1H)        8.93-9.10 (s, 2H);    -   3. 1H NMR (400 MHz, DMSO) δ ppm 1.54 (d, J=6.97 Hz, 3H) 5.04 (d,        J=6.60 Hz, 1H) 6.97-7.16 (m, 2H) 7.91-7.99 (m, 1H) 8.06-8.15 (m,        1H) 8.65 (d, J=2.93 Hz, 1H); 19F NMR (377 MHz, DMSO) δ ppm        −126.89 (s, 1 F)

The activity of the compositions according to the invention can bebroadened considerably, and adapted to prevailing circumstances, byadding other insecticidally, acaricidally and/or fungicidally activeingredients. The mixtures of the compounds of formula I with otherinsecticidally, acaricidally and/or fungicidally active ingredients mayalso have further surprising advantages which can also be described, ina wider sense, as synergistic activity. For example, better tolerance byplants, reduced phytotoxicity, insects can be controlled in theirdifferent development stages or better behaviour during theirproduction, for example during grinding or mixing, during their storageor during their use.

Suitable additions to active ingredients here are, for example,representatives of the following classes of active ingredients:organophosphorus compounds, nitrophenol derivatives, thioureas, juvenilehormones, formamidines, benzophenone derivatives, ureas, pyrrolederivatives, carbamates, pyrethroids, chlorinated hydrocarbons,acylureas, pyridylmethyleneamino derivatives, macrolides, neonicotinoidsand Bacillus thuringiensis preparations.

The following mixtures of a compound of formula I with an activesubstances are preferred (the abbreviation “TX” means “one compoundselected from the compounds defined in Tables D-1 to D-66 and Table P”):

an adjuvant selected from the group of substances consisting ofpetroleum oils (alternative name) (628)+TX,

an insect control active substance selected from Abamectin+TX,Acequinocyl+TX, Acetamiprid+TX, Acetoprole+TX, Acrinathrin+TX,Acynonapyr+TX, Afidopyropen+TX, Afoxolaner+TX, Alanycarb+TX,Allethrin+TX, Alpha-Cypermethrin+TX, Alphamethrin+TX, Amidoflumet+TX,Aminocarb+TX, Azocyclotin+TX, Bensultap+TX, Benzoximate+TX,Benzpyrimoxan+TX, Betacyfluthrin+TX, Beta-cypermethrin+TX,Bifenazate+TX, Bifenthrin+TX, Binapacryl+TX, Bioallethrin+TX,Bioallethrin S)-cyclopentylisomer+TX, Bioresmethrin+TX, Bistrifluron+TX,Broflanilide+TX, Brofluthrinate+TX, Bromophos-ethyl+TX, Buprofezine+TX,Butocarboxim+TX, Cadusafos+TX, Carbaryl+TX, Carbosulfan+TX, Cartap+TX,CAS number: 1472050-04-6+TX, CAS number: 1632218-00-8+TX, CAS number:1808115-49-2+TX, CAS number: 2032403-97-5+TX, CAS number:2044701-44-0+TX, CAS number: 2128706-05-6+TX, CAS number: 2249718-27-0(or CAS 2246757-58-2)+TX, CAS number: 907187-07-9+TX,Chlorantraniliprole+TX, Chlordane+TX, Chlorfenapyr+TX,Chloroprallethrin+TX, Chromafenozide+TX, Clenpirin+TX, Cloethocarb+TX,Clothianidin+TX, 2-chlorophenyl N-methylcarbamate (CPMC)+TX,Cyanofenphos+TX, Cyantraniliprole+TX, Cyclaniliprole+TX,Cyclobutrifluram+TX, Cycloprothrin+TX, Cycloxaprid+TX, Cycloxaprid+TX,Cyenopyrafen+TX, Cyetpyrafen+TX, Cyflumetofen+TX, Cyfluthrin+TX,Cyhalodiamide+TX, Cyhalothrin+TX, Cypermethrin+TX, Cyphenothrin+TX,Cyproflanilide+TX, Cyromazine+TX, Deltamethrin+TX, Diafenthiuron+TX,Dialifos+TX, Dibrom+TX, Dicloromezotiaz+TX, Diflovidazine+TX,Diflubenzuron+TX, dimpropyridaz+TX, Dinactin+TX, Dinocap+TX,Dinotefuran+TX, Dioxabenzofos+TX, Emamectin (Emamectin Benzoate)+TX,Empenthrin+TX, Epsilon−momfluorothrin+TX, Epsilon-metofluthrin+TX,Esfenvalerate+TX, Ethion+TX, Ethiprole+TX, Etofenprox+TX, Etoxazole+TX,Famphur+TX, Fenazaquin+TX, Fenfluthrin+TX, Fenitrothion+TX,Fenobucarb+TX, Fenothiocarb+TX, Fenoxycarb+TX, Fenpropathrin+TX,Fenpyroxymate+TX, Fensulfothion+TX, Fenthion+TX, Fentinacetate+TX,Fenvalerate+TX, Fipronil+TX, Flometoquin+TX, Flonicamid+TX,Fluacrypyrim+TX, Fluazaindolizine+TX, Fluazuron+TX, Flubendiamide+TX,Flubenzimine+TX, Flucitrinate+TX, Flucycloxuron+TX, Flucythrinate+TX,Fluensulfone+TX, Flufenerim+TX, Flufenprox+TX, Flufiprole+TX,Fluhexafon+TX, Flumethrin+TX, Fluopyram+TX, Flupentiofenox+TX,Flupyradifurone+TX, Flupyrimin+TX, Fluralaner+TX, Fluvalinate+TX,Fluxametamide+TX, Fosthiazate+TX, Gamma-Cyhalothrin+TX, Gossyplure™+TX,Guadipyr+TX, Halofenozide+TX, Halofenozide+TX, Halfenprox+TX,Heptafluthrin+TX, Hexythiazox+TX, Hydramethylnon+TX, Imicyafos+TX,Imidacloprid+TX, Imiprothrin+TX, Indoxacarb+TX, Iodomethane+TX,Iprodione+TX, Isocycloseram+TX, Isothioate+TX, Ivermectin+TX,Kappa-bifenthrin+TX, Kappa-tefluthrin+TX, Lambda-Cyhalothrin+TX,Lepimectin+TX, Lufenuron+TX, Metaflumizone+TX, Metaldehyde+TX, Metam+TX,Methomyl+TX, Methoxyfenozide+TX, Metofluthrin+TX, Metolcarb+TX,Mexacarbate+TX, Milbemectin+TX, Momfluorothrin+TX, Niclosamide+TX,Nicofluprole+TX; Nitenpyram+TX, Nithiazine+TX, Omethoate+TX, Oxamyl+TX,Oxazosulfyl+TX, Parathion-ethyl+TX, Permethrin+TX, Phenothrin+TX,Phosphocarb+TX, Piperonylbutoxide+TX, Pirimicarb+TX,Pirimiphos-ethyl+TX, Polyhedrosis virus+TX, Prallethrin+TX,Profenofos+TX, Profenofos+TX, Profluthrin+TX, Propargite+TX,Propetamphos+TX, Propoxur+TX, Prothiophos+TX, Protrifenbute+TX,Pyflubumide+TX, Pymetrozine+TX, Pyraclofos+TX, Pyrafluprole+TX,Pyridaben+TX, Pyridalyl+TX, Pyrifluquinazon+TX, Pyrimidifen+TX,Pyriminostrobin+TX, Pyriprole+TX, Pyriproxyfen+TX, Resmethrin+TX,Sarolaner+TX, Selamectin+TX, Silafluofen+TX, Spinetoram+TX, Spinosad+TX,Spirodiclofen+TX, Spiromesifen+TX, Spiropidion+TX, Spirotetramat+TX,Sulfoxaflor+TX, Tebufenozide+TX, Tebufenpyrad+TX, Tebupirimiphos+TX,Tefluthrin+TX, Temephos+TX, Tetrachlorantraniliprole+TX, Tetradiphon+TX,Tetramethrin+TX, Tetramethylfluthrin+TX, Tetranactin+TX,Tetraniliprole+TX, Theta-cypermethrin+TX, Thiacloprid+TX,Thiamethoxam+TX, Thiocyclam+TX, Thiodicarb+TX, Thiofanox+TX,Thiometon+TX, Thiosultap+TX, Tioxazafen+TX, Tolfenpyrad+TX,Toxaphene+TX, Tralomethrin+TX, Transfluthrin+TX, Triazamate+TX,Triazophos+TX, Trichlorfon+TX, Trichloronate+TX, Trichlorphon+TX,Triflumezopyrim+TX, Tyclopyrazoflor+TX, Zeta-Cypermethrin+TX, Extract ofseaweed and fermentation product derived from melasse+TX, Extract ofseaweed and fermentation product derived from melasse comprisingurea+TX, amino acids+TX, potassium and molybdenum and EDTA-chelatedmanganese+TX, Extract of seaweed and fermented plant products+TX,Extract of seaweed and fermented plant products comprisingphytohormones+TX, vitamins+TX, EDTA-chelated copper+TX, zinc+TX, andiron+TX, Azadirachtin+TX, Bacillus aizawai+TX, Bacillus chitinosporusAQ746 (NRRL Accession No B-21 618)+TX, Bacillus firmus+TX, Bacilluskurstaki+TX, Bacillus mycoides AQ726 (NRRL Accession No. B-21664)+TX,Bacillus pumilus (NRRL Accession No B-30087)+TX, Bacillus pumilus AQ717(NRRL Accession No. B-21662)+TX, Bacillus sp. AQ178 (ATCC Accession No.53522)+TX, Bacillus sp. AQ175 (ATCC Accession No. 55608)+TX, Bacillussp. AQ177 (ATCC Accession No. 55609)+TX, Bacillus subtilisunspecified+TX, Bacillus subtilis AQ153 (ATCC Accession No. 55614)+TX,Bacillus subtilis AQ30002 (NRRL Accession No. B-50421)+TX, Bacillussubtilis AQ30004 (NRRL Accession No. B-50455)+TX, Bacillus subtilisAQ713 (NRRL Accession No. B-21661)+TX, Bacillus subtilis AQ743 (NRRLAccession No. B-21665)+TX, Bacillus thuringiensis AQ52 (NRRL AccessionNo. B-21619)+TX, Bacillus thuringiensis BD #32 (NRRL Accession NoB-21530)+TX, Bacillus thuringiensis subspec. kurstaki BMP 123+TX,Beauveria bassiana+TX, D-limonene+TX, Granulovirus+TX, Harpin+TX,Helicoverpa armigera Nucleopolyhedrovirus+TX, Helicoverpa zeaNucleopolyhedrovirus+TX, Heliothis virescens Nucleopolyhedrovirus+TX,Heliothis punctigera Nucleopolyhedrovirus+TX, Metarhizium spp.+TX,Muscodor albus 620 (NRRL Accession No. 30547)+TX, Muscodor roseus A₃-5(NRRL Accession No. 30548)+TX, Neem tree based products+TX, Paecilomycesfumosoroseus+TX, Paecilomyces lilacinus+TX, Pasteuria nishizawae+TX,Pasteuria penetrans+TX, Pasteuria ramosa+TX, Pasteuria thornei+TX,Pasteuria usgae+TX, P-cymene+TX, Plutella xylostella Granulosisvirus+TX, Plutella xylostella Nucleopolyhedrovirus+TX, Polyhedrosisvirus+TX, pyrethrum+TX, QRD 420 (a terpenoid blend)+TX, QRD 452 (aterpenoid blend)+TX, QRD 460 (a terpenoid blend)+TX, Quillajasaponaria+TX, Rhodococcus globerulus AQ719 (NRRL Accession NoB-21663)+TX, Spodoptera frugiperda Nucleopolyhedrovirus+TX, Streptomycesgalbus (NRRL Accession No. 30232)+TX, Streptomyces sp. (NRRL AccessionNo. B-30145)+TX, Terpenoid blend+TX, and Verticillium spp.;

an algicide selected from the group of substances consisting ofbethoxazin [CCN]+TX, copper dioctanoate (IUPAC name) (170)+TX, coppersulfate (172)+TX, cybutryne [CCN]+TX, dichlone (1052)+TX, dichlorophen(232)+TX, endothal (295)+TX, fentin (347)+TX, hydrated lime [CCN]+TX,nabam (566)+TX, quinoclamine (714)+TX, quinonamid (1379)+TX, simazine(730)+TX, triphenyltin acetate (IUPAC name) (347) and triphenyltinhydroxide (IUPAC name) (347)+TX;

an anthelmintic selected from the group of substances consisting ofabamectin (1)+TX, crufomate (1011)+TX, Cyclobutrifluram+TX, doramectin(alternative name) [CCN]+TX, emamectin (291)+TX, emamectin benzoate(291)+TX, eprinomectin (alternative name) [CCN]+TX, ivermectin(alternative name) [CCN]+TX, milbemycin oxime (alternative name)[CCN]+TX, moxidectin (alternative name) [CCN]+TX, piperazine [CCN]+TX,selamectin (alternative name) [CCN]+TX, spinosad (737) and thiophanate(1435)+TX;

an avicide selected from the group of substances consisting ofchloralose (127)+TX, endrin (1122)+TX, fenthion (346)+TX,pyridin-4-amine (IUPAC name) (23) and strychnine (745)+TX;

a bactericide selected from the group of substances consisting of1-hydroxy-1H-pyridine-2-thione (IUPAC name) (1222)+TX,4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748)+TX,8-hydroxyquinoline sulfate (446)+TX, bronopol (97)+TX, copperdioctanoate (IUPAC name) (170)+TX, copper hydroxide (IUPAC name)(169)+TX, cresol [CCN]+TX, dichlorophen (232)+TX, dipyrithione(1105)+TX, dodicin (1112)+TX, fenaminosulf (1144)+TX, formaldehyde(404)+TX, hydrargaphen (alternative name) [CCN]+TX, kasugamycin(483)+TX, kasugamycin hydrochloride hydrate (483)+TX, nickelbis(dimethyldithiocarbamate) (IUPAC name) (1308)+TX, nitrapyrin(580)+TX, octhilinone (590)+TX, oxolinic acid (606)+TX, oxytetracycline(611)+TX, potassium hydroxyquinoline sulfate (446)+TX, probenazole(658)+TX, streptomycin (744)+TX, streptomycin sesquisulfate (744)+TX,tecloftalam (766)+TX, and thiomersal (alternative name) [CCN]+TX;

a biological agent selected from the group of substances consisting ofAdoxophyes orana GV (alternative name) (12)+TX, Agrobacteriumradiobacter (alternative name) (13)+TX, Amblyseius spp. (alternativename) (19)+TX, Anagrapha falcifera NPV (alternative name) (28)+TX,Anagrus atomus (alternative name) (29)+TX, Aphelinus abdominalis(alternative name) (33)+TX, Aphidius colemani (alternative name)(34)+TX, Aphidoletes aphidimyza (alternative name) (35)+TX, Autographacalifornica NPV (alternative name) (38)+TX, Bacillus firmus (alternativename) (48)+TX, Bacillus sphaericus Neide (scientific name) (49)+TX,Bacillus thuringiensis Berliner (scientific name) (51)+TX, Bacillusthuringiensis subsp. aizawai (scientific name) (51)+TX, Bacillusthuringiensis subsp. israelensis (scientific name) (51)+TX, Bacillusthuringiensis subsp. japonensis (scientific name) (51)+TX, Bacillusthuringiensis subsp. kurstaki (scientific name) (51)+TX, Bacillusthuringiensis subsp. tenebrionis (scientific name) (51)+TX, Beauveriabassiana (alternative name) (53)+TX, Beauveria brongniartii (alternativename) (54)+TX, Chrysoperla carnea (alternative name) (151)+TX,Cryptolaemus montrouzieri (alternative name) (178)+TX, Cydia pomonellaGV (alternative name) (191)+TX, Dacnusa sibirica (alternative name)(212)+TX, Diglyphus isaea (alternative name) (254)+TX, Encarsia formosa(scientific name) (293)+TX, Eretmocerus eremicus (alternative name)(300)+TX, Helicoverpa zea NPV (alternative name) (431)+TX,Heterorhabditis bacteriophora and H. megidis (alternative name)(433)+TX, Hippodamia convergens (alternative name) (442)+TX, Leptomastixdactylopii (alternative name) (488)+TX, Macrolophus caliginosus(alternative name) (491)+TX, Mamestra brassicae NPV (alternative name)(494)+TX, Metaphycus helvolus (alternative name) (522)+TX, Metarhiziumanisopliae var. acridum (scientific name) (523)+TX, Metarhiziumanisopliae var. anisopliae (scientific name) (523)+TX, Neodiprionsertifer NPV and N. lecontei NPV (alternative name) (575)+TX, Orius spp.(alternative name) (596)+TX, Paecilomyces fumosoroseus (alternativename) (613)+TX, Phytoseiulus persimilis (alternative name) (644)+TX,Spodoptera exigua multicapsid nuclear polyhedrosis virus (scientificname) (741)+TX, Steinernema bibionis (alternative name) (742)+TX,Steinernema carpocapsae (alternative name) (742)+TX, Steinernema feltiae(alternative name) (742)+TX, Steinernema glaseri (alternative name)(742)+TX, Steinernema riobrave (alternative name) (742)+TX, Steinernemariobravis (alternative name) (742)+TX, Steinernema scapterisci(alternative name) (742)+TX, Steinernema spp. (alternative name)(742)+TX, Trichogramma spp. (alternative name) (826)+TX, Typhlodromusoccidentalis (alternative name) (844) and Verticillium lecanii(alternative name) (848)+TX;

a soil sterilant selected from the group of substances consisting ofiodomethane (IUPAC name) (542) and methyl bromide (537)+TX;

a chemosterilant selected from the group of substances consisting ofapholate [CCN]+TX, bisazir (alternative name) [CCN]+TX, busulfan(alternative name) [CCN]+TX, diflubenzuron (250)+TX, dimatif(alternative name) [CCN]+TX, hemel [CCN]+TX, hempa [CCN]+TX, metepa[CCN]+TX, methiotepa [CCN]+TX, methyl apholate [CCN]+TX, morzid[CCN]+TX, penfluron (alternative name) [CCN]+TX, tepa [CCN]+TX,thiohempa (alternative name) [CCN]+TX, thiotepa (alternative name)[CCN]+TX, tretamine (alternative name) [CCN] and uredepa (alternativename) [CCN]+TX;

an insect pheromone selected from the group of substances consisting of(E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol (IUPAC name) (222)+TX,(E)-tridec-4-en-1-yl acetate (IUPAC name) (829)+TX,(E)-6-methylhept-2-en-4-ol (IUPAC name) (541)+TX,(E,Z)-tetradeca-4,10-dien-1-yl acetate (IUPAC name) (779)+TX,(Z)-dodec-7-en-1-yl acetate (IUPAC name) (285)+TX, (Z)-hexadec-11-enal(IUPAC name) (436)+TX, (Z)-hexadec-11-en-1-yl acetate (IUPAC name)(437)+TX, (Z)-hexadec-13-en-11-yn-1-yl acetate (IUPAC name) (438)+TX,(Z)-icos-13-en-10-one (IUPAC name) (448)+TX, (Z)-tetradec-7-en-1-al(IUPAC name) (782)+TX, (Z)-tetradec-9-en-1-ol (IUPAC name) (783)+TX,(Z)-tetradec-9-en-1-yl acetate (IUPAC name) (784)+TX,(7E,9Z)-dodeca-7,9-dien-1-yl acetate (IUPAC name) (283)+TX,(9Z,11E)-tetradeca-9,11-dien-1-yl acetate (IUPAC name) (780)+TX,(9Z,12E)-tetradeca-9,12-dien-1-yl acetate (IUPAC name) (781)+TX,14-methyloctadec-1-ene (IUPAC name) (545)+TX, 4-methylnonan-5-ol with4-methylnonan-5-one (IUPAC name) (544)+TX, alpha-multistriatin(alternative name) [CCN]+TX, brevicomin (alternative name) [CCN]+TX,codlelure (alternative name) [CCN]+TX, codlemone (alternative name)(167)+TX, cuelure (alternative name) (179)+TX, disparlure (277)+TX,dodec-8-en-1-yl acetate (IUPAC name) (286)+TX, dodec-9-en-1-yl acetate(IUPAC name) (287)+TX, dodeca-8+TX, 10-dien-1-yl acetate (IUPAC name)(284)+TX, dominicalure (alternative name) [CCN]+TX, ethyl4-methyloctanoate (IUPAC name) (317)+TX, eugenol (alternative name)[CCN]+TX, frontalin (alternative name) [CCN]+TX, gossyplure (alternativename) (420)+TX, grandlure (421)+TX, grandlure I (alternative name)(421)+TX, grandlure II (alternative name) (421)+TX, grandlure III(alternative name) (421)+TX, grandlure IV (alternative name) (421)+TX,hexalure [CCN]+TX, ipsdienol (alternative name) [CCN]+TX, ipsenol(alternative name) [CCN]+TX, japonilure (alternative name) (481)+TX,lineatin (alternative name) [CCN]+TX, litlure (alternative name)[CCN]+TX, looplure (alternative name) [CCN]+TX, medlure [CCN]+TX,megatomoic acid (alternative name) [CCN]+TX, methyl eugenol (alternativename) (540)+TX, muscalure (563)+TX, octadeca-2,13-dien-1-yl acetate(IUPAC name) (588)+TX, octadeca-3,13-dien-1-yl acetate (IUPAC name)(589)+TX, orfralure (alternative name) [CCN]+TX, oryctalure (alternativename) (317)+TX, ostramone (alternative name) [CCN]+TX, siglure [CCN]+TX,sordidin (alternative name) (736)+TX, sulcatol (alternative name)[CCN]+TX, tetradec-11-en-1-yl acetate (IUPAC name) (785)+TX, trimedlure(839)+TX, trimedlure A (alternative name) (839)+TX, trimedlure B₁(alternative name) (839)+TX, trimedlure B₂ (alternative name) (839)+TX,trimedlure C (alternative name) (839) and trunc-call (alternative name)[CCN]+TX;

an insect repellent selected from the group of substances consisting of2-(octylthio)ethanol (IUPAC name) (591)+TX, butopyronoxyl (933)+TX,butoxy(polypropylene glycol) (936)+TX, dibutyl adipate (IUPAC name)(1046)+TX, dibutyl phthalate (1047)+TX, dibutyl succinate (IUPAC name)(1048)+TX, diethyltoluamide [CCN]+TX, dimethyl carbate [CCN]+TX,dimethyl phthalate [CCN]+TX, ethyl hexanediol (1137)+TX, hexamide[CCN]+TX, methoquin-butyl (1276)+TX, methylneodecanamide [CCN]+TX,oxamate [CCN] and picaridin [CCN]+TX;

a molluscicide selected from the group of substances consisting ofbis(tributyltin) oxide (IUPAC name) (913)+TX, bromoacetamide [CCN]+TX,calcium arsenate [CCN]+TX, cloethocarb (999)+TX, copper acetoarsenite[CCN]+TX, copper sulfate (172)+TX, fentin (347)+TX, ferric phosphate(IUPAC name) (352)+TX, metaldehyde (518)+TX, methiocarb (530)+TX,niclosamide (576)+TX, niclosamide-olamine (576)+TX, pentachlorophenol(623)+TX, sodium pentachlorophenoxide (623)+TX, tazimcarb (1412)+TX,thiodicarb (799)+TX, tributyltin oxide (913)+TX, trifenmorph (1454)+TX,trimethacarb (840)+TX, triphenyltin acetate (IUPAC name) (347) andtriphenyltin hydroxide (IUPAC name) (347)+TX, pyriprole[394730-71-3]+TX;

a nematicide selected from the group of substances consisting ofAKD-3088 (compound code)+TX, 1,2-dibromo-3-chloropropane (IUPAC/ChemicalAbstracts name) (1045)+TX, 1,2-dichloropropane (IUPAC/Chemical Abstractsname) (1062)+TX, 1,2-dichloropropane with 1,3-dichloropropene (IUPACname) (1063)+TX, 1,3-dichloropropene (233)+TX,3,4-dichlorotetrahydrothiophene 1,1-dioxide (IUPAC/Chemical Abstractsname) (1065)+TX, 3-(4-chlorophenyl)-5-methylrhodanine (IUPAC name)(980)+TX, 5-methyl-6-thioxo-1,3,5-thiadiazinan-3-ylacetic acid (IUPACname) (1286)+TX, 6-isopentenylaminopurine (alternative name) (210)+TX,abamectin (1)+TX, acetoprole [CCN]+TX, alanycarb (15)+TX, aldicarb(16)+TX, aldoxycarb (863)+TX, AZ 60541 (compound code)+TX, benclothiaz[CCN]+TX, benomyl (62)+TX, butylpyridaben (alternative name)+TX,cadusafos (109)+TX, carbofuran (118)+TX, carbon disulfide (945)+TX,carbosulfan (119)+TX, chloropicrin (141)+TX, chlorpyrifos (145)+TX,cloethocarb (999)+TX, Cyclobutrifluram+TX, cytokinins (alternative name)(210)+TX, dazomet (216)+TX, DBCP (1045)+TX, DCIP (218)+TX, diamidafos(1044)+TX, dichlofenthion (1051)+TX, dicliphos (alternative name)+TX,dimethoate (262)+TX, doramectin (alternative name) [CCN]+TX, emamectin(291)+TX, emamectin benzoate (291)+TX, eprinomectin (alternative name)[CCN]+TX, ethoprophos (312)+TX, ethylene dibromide (316)+TX, fenamiphos(326)+TX, fenpyrad (alternative name)+TX, fensulfothion (1158)+TX,fosthiazate (408)+TX, fosthietan (1196)+TX, furfural (alternative name)[CCN]+TX, GY-81 (development code) (423)+TX, heterophos [CCN]+TX,iodomethane (IUPAC name) (542)+TX, isamidofos (1230)+TX, isazofos(1231)+TX, ivermectin (alternative name) [CCN]+TX, kinetin (alternativename) (210)+TX, mecarphon (1258)+TX, metam (519)+TX, metam-potassium(alternative name) (519)+TX, metam-sodium (519)+TX, methyl bromide(537)+TX, methyl isothiocyanate (543)+TX, milbemycin oxime (alternativename) [CCN]+TX, moxidectin (alternative name) [CCN]+TX, Myrotheciumverrucaria composition (alternative name) (565)+TX, NC-184 (compoundcode)+TX, oxamyl (602)+TX, phorate (636)+TX, phosphamidon (639)+TX,phosphocarb [CCN]+TX, sebufos (alternative name)+TX, selamectin(alternative name) [CCN]+TX, spinosad (737)+TX, terbam (alternativename)+TX, terbufos (773)+TX, tetrachlorothiophene (IUPAC/ChemicalAbstracts name) (1422)+TX, thiafenox (alternative name)+TX, thionazin(1434)+TX, triazophos (820)+TX, triazuron (alternative name)+TX,xylenols [CCN]+TX, YI-5302 (compound code) and zeatin (alternative name)(210)+TX, fluensulfone [318290-98-1]+TX, fluopyram+TX;

a nitrification inhibitor selected from the group of substancesconsisting of potassium ethylxanthate [CCN] and nitrapyrin (580)+TX;

a plant activator selected from the group of substances consisting ofacibenzolar (6)+TX, acibenzolar-S-methyl (6)+TX, probenazole (658) andReynoutria sachalinensis extract (alternative name) (720)+TX;

a rodenticide selected from the group of substances consisting of2-isovalerylindan-1,3-dione (IUPAC name) (1246)+TX,4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748)+TX,alpha-chlorohydrin [CCN]+TX, aluminium phosphide (640)+TX, antu(880)+TX, arsenous oxide (882)+TX, barium carbonate (891)+TX,bisthiosemi (912)+TX, brodifacoum (89)+TX, bromadiolone (includingalpha-bromadiolone)+TX, bromethalin (92)+TX, calcium cyanide (444)+TX,chloralose (127)+TX, chlorophacinone (140)+TX, cholecalciferol(alternative name) (850)+TX, coumachlor (1004)+TX, coumafuryl (1005)+TX,coumatetralyl (175)+TX, crimidine (1009)+TX, difenacoum (246)+TX,difethialone (249)+TX, diphacinone (273)+TX, ergocalciferol (301)+TX,flocoumafen (357)+TX, fluoroacetamide (379)+TX, flupropadine (1183)+TX,flupropadine hydrochloride (1183)+TX, gamma-HCH (430)+TX, HCH (430)+TX,hydrogen cyanide (444)+TX, iodomethane (IUPAC name) (542)+TX, lindane(430)+TX, magnesium phosphide (IUPAC name) (640)+TX, methyl bromide(537)+TX, norbormide (1318)+TX, phosacetim (1336)+TX, phosphine (IUPACname) (640)+TX, phosphorus [CCN]+TX, pindone (1341)+TX, potassiumarsenite [CCN]+TX, pyrinuron (1371)+TX, scilliroside (1390)+TX, sodiumarsenite [CCN]+TX, sodium cyanide (444)+TX, sodium fluoroacetate(735)+TX, strychnine (745)+TX, thallium sulfate [CCN]+TX, warfarin (851)and zinc phosphide (640)+TX;

a synergist selected from the group of substances consisting of2-(2-butoxyethoxy)ethyl piperonylate (IUPAC name) (934)+TX,5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone (IUPAC name) (903)+TX,farnesol with nerolidol (alternative name) (324)+TX, MB-599 (developmentcode) (498)+TX, MGK 264 (development code) (296)+TX, piperonyl butoxide(649)+TX, piprotal (1343)+TX, propyl isomer (1358)+TX, S421 (developmentcode) (724)+TX, sesamex (1393)+TX, sesasmolin (1394) and sulfoxide(1406)+TX;

an animal repellent selected from the group of substances consisting ofanthraquinone (32)+TX, chloralose (127)+TX, copper naphthenate [CCN]+TX,copper oxychloride (171)+TX, diazinon (227)+TX, dicyclopentadiene(chemical name) (1069)+TX, guazatine (422)+TX, guazatine acetates(422)+TX, methiocarb (530)+TX, pyridin-4-amine (IUPAC name) (23)+TX,thiram (804)+TX, trimethacarb (840)+TX, zinc naphthenate [CCN] and ziram(856)+TX;

a virucide selected from the group of substances consisting of imanin(alternative name) [CCN] and ribavirin (alternative name) [CCN]+TX; awound protectant selected from the group of substances consisting ofmercuric oxide (512)+TX, octhilinone (590) and thiophanate-methyl(802)+TX;

a biologically active substance selected from1,1-bis(4-chlorophenyl)-2-ethoxyethanol+TX, 2,4-dichlorophenylbenzenesulfonate+TX, 2-fluoro-N-methyl-N-1-naphthylacetamide+TX,4-chlorophenyl phenyl sulfone+TX, acetoprole+TX, aldoxycarb+TX,amidithion+TX, amidothioate+TX, amiton+TX, amiton hydrogen oxalate+TX,amitraz+TX, aramite+TX, arsenous oxide+TX, azobenzene+TX, azothoate+TX,benomyl+TX, benoxafos+TX, benzyl benzoate+TX, bixafen+TX,brofenvalerate+TX, bromocyclen+TX, bromophos+TX, bromopropylate+TX,buprofezin+TX, butocarboxim+TX, butoxycarboxim+TX, butylpyridaben+TX,calcium polysulfide+TX, camphechlor+TX, carbanolate+TX,carbophenothion+TX, cymiazole+TX, chinomethionat+TX, chlorbenside+TX,chlordimeform+TX, chlordimeform hydrochloride+TX, chlorfenethol+TX,chlorfenson+TX, chlorfensulfide+TX, chlorobenzilate+TX,chloromebuform+TX, chloromethiuron+TX, chloropropylate+TX,chlorthiophos+TX, cinerin I+TX, cinerin II+TX, cinerins+TX,closantel+TX, coumaphos+TX, crotamiton+TX, crotoxyphos+TX, cufraneb+TX,cyanthoate+TX, DCPM+TX, DDT+TX, demephion+TX, demephion-O+TX,demephion-S+TX, demeton-methyl+TX, demeton-O+TX, demeton-O-methyl+TX,demeton-S+TX, demeton-S-methyl+TX, demeton-S-methylsulfon+TX,dichlofluanid+TX, dichlorvos+TX, dicliphos+TX, dienochlor+TX,dimefox+TX, dinex+TX, dinex-diclexine+TX, dinocap-4+TX, dinocap-6+TX,dinocton+TX, dinopenton+TX, dinosulfon+TX, dinoterbon+TX, dioxathion+TX,diphenyl sulfone+TX, disulfiram+TX, DNOC+TX, dofenapyn+TX,doramectin+TX, endothion+TX, eprinomectin+TX, ethoate-methyl+TX,etrimfos+TX, fenazaflor+TX, fenbutatin oxide+TX, fenothiocarb+TX,fenpyrad+TX, fenpyroximate+TX, fenpyrazamine+TX, fenson+TX,fentrifanil+TX, flubenzimine+TX, flucycloxuron+TX, fluenetil+TX,fluorbenside+TX, FMC 1137+TX, formetanate+TX, formetanatehydrochloride+TX, formparanate+TX, gamma-HCH+TX, glyodin+TX,halfenprox+TX, hexadecyl cyclopropanecarboxylate+TX, isocarbophos+TX,jasmolin I+TX, jasmolin II+TX, jodfenphos+TX, lindane+TX, malonoben+TX,mecarbam+TX, mephosfolan+TX, mesulfen+TX, methacrifos+TX, methylbromide+TX, metolcarb+TX, mexacarbate+TX, milbemycin oxime+TX,mipafox+TX, monocrotophos+TX, morphothion+TX, moxidectin+TX, naled+TX,4-chloro-2-(2-chloro-2-methyl-propyl)-5-[(6-iodo-3-pyridyl)methoxy]pyridazin-3-one+TX,nifluridide+TX, nikkomycins+TX, nitrilacarb+TX, nitrilacarb 1:1 zincchloride complex+TX, omethoate+TX, oxydeprofos+TX, oxydisulfoton+TX,pp′-DDT+TX, parathion+TX, permethrin+TX, phenkapton+TX, phosalone+TX,phosfolan+TX, phosphamidon+TX, polychloroterpenes+TX, polynactins+TX,proclonol+TX, promacyl+TX, propoxur+TX, prothidathion+TX, prothoate+TX,pyrethrin I+TX, pyrethrin II+TX, pyrethrins+TX, pyridaphenthion+TX,pyrimitate+TX, quinalphos+TX, quintiofos+TX, R-1492+TX, phosglycin+TX,rotenone+TX, schradan+TX, sebufos+TX, selamectin+TX, sophamide+TX,SSI-121+TX, sulfiram+TX, sulfluramid+TX, sulfotep+TX, sulfur+TX,diflovidazin+TX, tau-fluvalinate+TX, TEPP+TX, terbam+TX, tetradifon+TX,tetrasul+TX, thiafenox+TX, thiocarboxime+TX, thiofanox+TX, thiometon+TX,thioquinox+TX, thuringiensin+TX, triamiphos+TX, triarathene+TX,triazophos+TX, triazuron+TX, trifenofos+TX, trinactin+TX,vamidothion+TX, vaniliprole+TX, bethoxazin+TX, copper dioctanoate+TX,copper sulfate+TX, cybutryne+TX, dichlone+TX, dichlorophen+TX,endothal+TX, fentin+TX, hydrated lime+TX, nabam+TX, quinoclamine+TX,quinonamid+TX, simazine+TX, triphenyltin acetate+TX, triphenyltinhydroxide+TX, crufomate+TX, piperazine+TX, thiophanate+TX,chloralose+TX, fenthion+TX, pyridin-4-amine+TX, strychnine+TX,1-hydroxy-1H-pyridine-2-thione+TX,4-(quinoxalin-2-ylamino)benzenesulfonamide+TX, 8-hydroxyquinolinesulfate+TX, bronopol+TX, copper hydroxide+TX, cresol+TX,dipyrithione+TX, dodicin+TX, fenaminosulf+TX, formaldehyde+TX,hydrargaphen+TX, kasugamycin+TX, kasugamycin hydrochloride hydrate+TX,nickel bis(dimethyldithiocarbamate)+TX, nitrapyrin+TX, octhilinone+TX,oxolinic acid+TX, oxytetracycline+TX, potassium hydroxyquinolinesulfate+TX, probenazole+TX, streptomycin+TX, streptomycinsesquisulfate+TX, tecloftalam+TX, thiomersal+TX, Adoxophyes orana GV+TX,Agrobacterium radiobacter+TX, Amblyseius spp.+TX, Anagrapha falciferaNPV+TX, Anagrus atomus+TX, Aphelinus abdominalis+TX, Aphidiuscolemani+TX, Aphidoletes aphidimyza+TX, Autographa californica NPV+TX,Bacillus sphaericus Neide+TX, Beauveria brongniartii+TX, Chrysoperlacarnea+TX, Cryptolaemus montrouzieri+TX, Cydia pomonella GV+TX, Dacnusasibirica+TX, Diglyphus isaea+TX, Encarsia formosa+TX, Eretmoceruseremicus+TX, Heterorhabditis bacteriophora and H. megidis+TX, Hippodamiaconvergens+TX, Leptomastix dactylopii+TX, Macrolophus caliginosus+TX,Mamestra brassicae NPV+TX, Metaphycus helvolus+TX, Metarhiziumanisopliae var. acridum+TX, Metarhizium anisopliae var. anisopliae+TX,Neodiprion sertifer NPV and N. lecontei NPV+TX, Orius spp.+TX,Paecilomyces fumosoroseus+TX, Phytoseiulus persimilis+TX, Steinernemabibionis+TX, Steinernema carpocapsae+TX, Steinernema feltiae+TX,Steinernema glaseri+TX, Steinernema riobrave+TX, Steinernemariobravis+TX, Steinernema scapterisci+TX, Steinernema spp.+TX,Trichogramma spp.+TX, Typhlodromus occidentalis+TX, Verticilliumlecanii+TX, apholate+TX, bisazir+TX, busulfan+TX, dimatif+TX, hemel+TX,hempa+TX, metepa+TX, methiotepa+TX, methyl apholate+TX, morzid+TX,penfluron+TX, tepa+TX, thiohempa+TX, thiotepa+TX, tretamine+TX,uredepa+TX, (E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol+TX,(E)-tridec-4-en-1-yl acetate+TX, (E)-6-methylhept-2-en-4-ol+TX,(E,Z)-tetradeca-4,10-dien-1-yl acetate+TX, (Z)-dodec-7-en-1-ylacetate+TX, (Z)-hexadec-11-enal+TX, (Z)-hexadec-11-en-1-yl acetate+TX,(Z)-hexadec-13-en-11-yn-1-yl acetate+TX, (Z)-icos-13-en-10-one+TX,(Z)-tetradec-7-en-1-al+TX, (Z)-tetradec-9-en-1-ol+TX,(Z)-tetradec-9-en-1-yl acetate+TX, (7E,9Z)-dodeca-7,9-dien-1-ylacetate+TX, (9Z,11E)-tetradeca-9,11-dien-1-yl acetate+TX,(9Z,12E)-tetradeca-9,12-dien-1-yl acetate+TX, 14-methyloctadec-1-ene+TX,4-methylnonan-5-ol with 4-methylnonan-5-one+TX, alpha-multistriatin+TX,brevicomin+TX, codlelure+TX, codlemone+TX, cuelure+TX, disparlure+TX,dodec-8-en-1-yl acetate+TX, dodec-9-en-1-yl acetate+TX, dodeca-8+TX,10-dien-1-yl acetate+TX, dominicalure+TX, ethyl 4-methyloctanoate+TX,eugenol+TX, frontalin+TX, grandlure+TX, grandlure I+TX, grandlure II+TX,grandlure III+TX, grandlure IV+TX, hexalure+TX, ipsdienol+TX,ipsenol+TX, japonilure+TX, lineatin+TX, litlure+TX, looplure+TX,medlure+TX, megatomoic acid+TX, methyl eugenol+TX, muscalure+TX,octadeca-2,13-dien-1-yl acetate+TX, octadeca-3,13-dien-1-yl acetate+TX,orfralure+TX, oryctalure+TX, ostramone+TX, siglure+TX, sordidin+TX,sulcatol+TX, tetradec-11-en-1-yl acetate+TX, trimedlure+TX, trimedlureA+TX, trimedlure B₁+TX, trimedlure B₂+TX, trimedlure C+TX,trunc-call+TX, 2-(octylthio)ethanol+TX, butopyronoxyl+TX,butoxy(polypropylene glycol)+TX, dibutyl adipate+TX, dibutylphthalate+TX, dibutyl succinate+TX, diethyltoluamide+TX, dimethylcarbate+TX, dimethyl phthalate+TX, ethyl hexanediol+TX, hexamide+TX,methoquin-butyl+TX, methylneodecanamide+TX, oxamate+TX, picaridin+TX,1-dichloro-1-nitroethane+TX,1,1-dichloro-2,2-bis(4-ethylphenyl)ethane+TX, 1,2-dichloropropane with1,3-dichloropropene+TX, 1-bromo-2-chloroethane+TX,2,2,2-trichloro-1-(3,4-dichlorophenyl)ethyl acetate+TX,2,2-dichlorovinyl 2-ethylsulfinylethyl methyl phosphate+TX,2-(1,3-dithiolan-2-yl)phenyl dimethylcarbamate+TX,2-(2-butoxyethoxy)ethyl thiocyanate+TX,2-(4,5-dimethyl-1,3-dioxolan-2-yl)phenyl methylcarbamate+TX,2-(4-chloro-3,5-xylyloxy)ethanol+TX, 2-chlorovinyl diethyl phosphate+TX,2-imidazolidone+TX, 2-isovalerylindan-1,3-dione+TX,2-methyl(prop-2-ynyl)aminophenyl methylcarbamate+TX, 2-thiocyanatoethyllaurate+TX, 3-bromo-1-chloroprop-1-ene+TX, 3-methyl-1-phenylpyrazol-5-yldimethylcarbamate+TX, 4-methyl(prop-2-ynyl)amino-3,5-xylylmethylcarbamate+TX, 5,5-dimethyl-3-oxocyclohex-1-enyldimethylcarbamate+TX, acethion+TX, acrylonitrile+TX, aldrin+TX,allosamidin+TX, allyxycarb+TX, alpha-ecdysone+TX, aluminiumphosphide+TX, aminocarb+TX, anabasine+TX, athidathion+TX,azamethiphos+TX, Bacillus thuringiensis delta endotoxins+TX, bariumhexafluorosilicate+TX, barium polysulfide+TX, barthrin+TX, Bayer22/190+TX, Bayer 22408+TX, beta-cyfluthrin+TX, beta-cypermethrin+TX,bioethanomethrin+TX, biopermethrin+TX, bis(2-chloroethyl) ether+TX,borax+TX, bromfenvinfos+TX, bromo-DDT+TX, bufencarb+TX, butacarb+TX,butathiofos+TX, butonate+TX, calcium arsenate+TX, calcium cyanide+TX,carbon disulfide+TX, carbon tetrachloride+TX, cartap hydrochloride+TX,cevadine+TX, chlorbicyclen+TX, chlordane+TX, chlordecone+TX,chloroform+TX, chloropicrin+TX, chlorphoxim+TX, chlorprazophos+TX,cis-resmethrin+TX, cismethrin+TX, clocythrin+TX, copperacetoarsenite+TX, copper arsenate+TX, copper oleate+TX, coumithoate+TX,cryolite+TX, CS 708+TX, cyanofenphos+TX, cyanophos+TX, cyclethrin+TX,cythioate+TX, d-tetramethrin+TX, DAEP+TX, dazomet+TX, decarbofuran+TX,diamidafos+TX, dicapthon+TX, dichlofenthion+TX, dicresyl+TX,dicyclanil+TX, dieldrin+TX, diethyl 5-methylpyrazol-3-yl phosphate+TX,dilor+TX, dimefluthrin+TX, dimetan+TX, dimethrin+TX, dimethylvinphos+TX,dimetilan+TX, dinoprop+TX, dinosam+TX, dinoseb+TX, diofenolan+TX,dioxabenzofos+TX, dithicrofos+TX, DSP+TX, ecdysterone+TX, EI 1642+TX,EMPC+TX, EPBP+TX, etaphos+TX, ethiofencarb+TX, ethyl formate+TX,ethylene dibromide+TX, ethylene dichloride+TX, ethylene oxide+TX,EXD+TX, fenchlorphos+TX, fenethacarb+TX, fenitrothion+TX, fenoxacrim+TX,fenpirithrin+TX, fensulfothion+TX, fenthion-ethyl+TX, flucofuron+TX,fosmethilan+TX, fospirate+TX, fosthietan+TX, furathiocarb+TX,furethrin+TX, guazatine+TX, guazatine acetates+TX, sodiumtetrathiocarbonate+TX, halfenprox+TX, HCH+TX, HEOD+TX, heptachlor+TX,heterophos+TX, HHDN+TX, hydrogen cyanide+TX, hyquincarb+TX, IPSP+TX,isazofos+TX, isobenzan+TX, isodrin+TX, isofenphos+TX, isolane+TX,isoprothiolane+TX, isoxathion+TX, juvenile hormone I+TX, juvenilehormone II+TX, juvenile hormone III+TX, kelevan+TX, kinoprene+TX, leadarsenate+TX, leptophos+TX, lirimfos+TX, lythidathion+TX, m-cumenylmethylcarbamate+TX, magnesium phosphide+TX, mazidox+TX, mecarphon+TX,menazon+TX, mercurous chloride+TX, mesulfenfos+TX, metam+TX,metam-potassium+TX, metam-sodium+TX, methanesulfonyl fluoride+TX,methocrotophos+TX, methoprene+TX, methothrin+TX, methoxychlor+TX, methylisothiocyanate+TX, methylchloroform+TX, methylene chloride+TX,metoxadiazone+TX, mirex+TX, naftalofos+TX, naphthalene+TX, NC-170+TX,nicotine+TX, nicotine sulfate+TX, nithiazine+TX, nornicotine+TX,O-5-dichloro-4-iodophenyl O-ethyl ethylphosphonothioate+TX, O,O-diethylO-4-methyl-2-oxo-2H-chromen-7-yl phosphorothioate+TX, O,O-diethylO-6-methyl-2-propylpyrimidin-4-yl phosphorothioate+TX,O,O,O′,O′-tetrapropyl dithiopyrophosphate+TX, oleic acid+TX,para-dichlorobenzene+TX, parathion-methyl+TX, pentachlorophenol+TX,pentachlorophenyl laurate+TX, PH 60-38+TX, phenkapton+TX,phosnichlor+TX, phosphine+TX, phoxim-methyl+TX, pirimetaphos+TX,polychlorodicyclopentadiene isomers+TX, potassium arsenite+TX, potassiumthiocyanate+TX, precocene I+TX, precocene II+TX, precocene III+TX,primidophos+TX, profluthrin+TX, promecarb+TX, prothiofos+TX,pyrazophos+TX, pyresmethrin+TX, quassia+TX, quinalphos-methyl+TX,quinothion+TX, rafoxanide+TX, resmethrin+TX, rotenone+TX, kadethrin+TX,ryania+TX, ryanodine+TX, sabadilla)+TX, schradan+TX, sebufos+TX,SI-0009+TX, thiapronil+TX, sodium arsenite+TX, sodium cyanide+TX, sodiumfluoride+TX, sodium hexafluorosilicate+TX, sodiumpentachlorophenoxide+TX, sodium selenate+TX, sodium thiocyanate+TX,sulcofuron+TX, sulcofuron-sodium+TX, sulfuryl fluoride+TX, sulprofos+TX,tar oils+TX, tazimcarb+TX, TDE+TX, tebupirimfos+TX, temephos+TX,terallethrin+TX, tetrachloroethane+TX, thicrofos+TX, thiocyclam+TX,thiocyclam hydrogen oxalate+TX, thionazin+TX, thiosultap+TX,thiosultap-sodium+TX, tralomethrin+TX, transpermethrin+TX,triazamate+TX, trichlormetaphos-3+TX, trichloronat+TX, trimethacarb+TX,tolprocarb+TX, triclopyricarb+TX, triprene+TX, veratridine+TX,veratrine+TX, XMC+TX, zetamethrin+TX, zinc phosphide+TX, zolaprofos+TX,and meperfluthrin+TX, tetramethylfluthrin+TX, bis(tributyltin) oxide+TX,bromoacetamide+TX, ferric phosphate+TX, niclosamide-olamine+TX,tributyltin oxide+TX, pyrimorph+TX, trifenmorph+TX,1,2-dibromo-3-chloropropane+TX, 1,3-dichloropropene+TX,3,4-dichlorotetrahydrothiophene 1,1-dioxide+TX,3-(4-chlorophenyl)-5-methylrhodanine+TX,5-methyl-6-thioxo-1,3,5-thiadiazinan-3-ylacetic acid+TX,6-isopentenylaminopurine+TX,2-fluoro-N-(3-methoxyphenyl)-9H-purin-6-amine+TX, benclothiaz+TX,cytokinins+TX, DCIP+TX, furfural+TX, isamidofos+TX, kinetin+TX,Myrothecium verrucaria composition+TX, tetrachlorothiophene+TX,xylenols+TX, zeatin+TX, potassium ethylxanthate+TX,acibenzolar+TX,acibenzolar-S-methyl+TX, Reynoutria sachalinensis extract+TX,alpha-chlorohydrin+TX, antu+TX, barium carbonate+TX, bisthiosemi+TX,brodifacoum+TX, bromadiolone (including alpha-bromadiolone)+TX,bromethalin+TX, chlorophacinone+TX, cholecalciferol+TX, coumachlor+TX,coumafuryl+TX, coumatetralyl+TX, crimidine+TX, difenacoum+TX,difethialone+TX, diphacinone+TX, ergocalciferol+TX, flocoumafen+TX,fluoroacetamide+TX, flupropadine+TX, flupropadine hydrochloride+TX,norbormide+TX, phosacetim+TX, phosphorus+TX, pindone+TX, pyrinuron+TX,scilliroside+TX, sodium fluoroacetate+TX, thallium sulfate+TX,warfarin+TX, 2-(2-butoxyethoxy)ethyl piperonylate+TX,5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone+TX, farnesol withnerolidol+TX, verbutin+TX, MGK 264+TX, piperonyl butoxide+TX,piprotal+TX, propyl isomer+TX, S421+TX, sesamex+TX, sesasmolin+TX,sulfoxide+TX, anthraquinone+TX, copper naphthenate+TX, copperoxychloride+TX, dicyclopentadiene+TX, thiram+TX, zinc naphthenate+TX,ziram+TX, imanin+TX, ribavirin+TX, mercuric oxide+TX,thiophanate-methyl+TX, azaconazole+TX, bitertanol+TX, bromuconazole+TX,cyproconazole+TX, difenoconazole+TX, diniconazole+TX, epoxiconazole+TX,fenbuconazole+TX, fluquinconazole+TX, flusilazole+TX, flutriafol+TX,furametpyr+TX, hexaconazole+TX, imazalil+TX, imiben-conazole+TX,ipconazole+TX, metconazole+TX, myclobutanil+TX, paclobutrazole+TX,pefurazoate+TX, penconazole+TX, prothioconazole+TX, pyrifenox+TX,prochloraz+TX, propiconazole+TX, pyrisoxazole+TX, simeconazole+TX,tebuconazole+TX, tetraconazole+TX, triadimefon+TX, triadimenol+TX,triflumizole+TX, triticonazole+TX, ancymidol+TX, fenarimol+TX,nuarimol+TX, bupirimate+TX, dimethirimol+TX, ethirimol+TX, dodemorph+TX,fenpropidin+TX, fenpropimorph+TX, spiroxamine+TX, tridemorph+TX,cyprodinil+TX, mepanipyrim+TX, pyrimethanil+TX, fenpiclonil+TX,fludioxonil+TX, benalaxyl+TX, furalaxyl+TX, metalaxyl-+TX,R-metalaxyl+TX, ofurace+TX, oxadixyl+TX, carbendazim+TX, debacarb+TX,fuberidazole+TX, thiabendazole+TX, chlozolinate+TX, dichlozoline+TX,myclozoline+TX, procymidone+TX, vinclozoline+TX, boscalid+TX,carboxin+TX, fenfuram+TX, flutolanil+TX, mepronil+TX, oxycarboxin+TX,penthiopyrad+TX, thifluzamide+TX, dodine+TX, iminoctadine+TX,azoxystrobin+TX, dimoxystrobin+TX, enestroburin+TX, fenaminstrobin+TX,flufenoxystrobin+TX, fluoxastrobin+TX, kresoxim-methyl+TX,metominostrobin+TX, trifloxystrobin+TX, orysastrobin+TX,picoxystrobin+TX, pyraclostrobin+TX, pyrametostrobin+TX,pyraoxystrobin+TX, ferbam+TX, mancozeb+TX, maneb+TX, metiram+TX,propineb+TX, zineb+TX, captafol+TX, captan+TX, fluoroimide+TX,folpet+TX, tolylfluanid+TX, bordeaux mixture+TX, copper oxide+TX,mancopper+TX, oxine-copper+TX, nitrothal-isopropyl+TX, edifenphos+TX,iprobenphos+TX, phosdiphen+TX, tolclofos-methyl+TX, anilazine+TX,benthiavalicarb+TX, blasticidin-S+TX, chloroneb+TX, chlorothalonil+TX,cyflufenamid+TX, cymoxanil+TX, cyclobutrifluram+TX, diclocymet+TX,diclomezine+TX, dicloran+TX, diethofencarb+TX, dimethomorph+TX,flumorph+TX, dithianon+TX, ethaboxam+TX, etridiazole+TX, famoxadone+TX,fenamidone+TX, fenoxanil+TX, ferimzone+TX, fluazinam+TX,fluopicolide+TX, flusulfamide+TX, fluxapyroxad+TX, fenhexamid+TX,fosetyl-aluminium+TX, hymexazol+TX, iprovalicarb+TX, cyazofamid+TX,methasulfocarb+TX, metrafenone+TX, pencycuron+TX, phthalide+TX,polyoxins+TX, propamocarb+TX, pyribencarb+TX, proquinazid+TX,pyroquilon+TX, pyriofenone+TX, quinoxyfen+TX, quintozene+TX,tiadinil+TX, triazoxide+TX, tricyclazole+TX, triforine+TX,validamycin+TX, valifenalate+TX, zoxamide+TX, mandipropamid+TX,flubeneteram+TX, isopyrazam+TX, sedaxane+TX, benzovindiflupyr+TX,pydiflumetofen+TX, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylicacid (3′,4′,5′-trifluoro-biphenyl-2-yl)-amide+TX, isoflucypram+TX,isotianil+TX, dipymetitrone+TX,6-ethyl-5,7-dioxo-pyrrolo[4,5][1,4]dithiino[1,2-c]isothiazole-3-carbonitrile+TX,2-(difluoromethyl)-N-[3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide+TX,4-(2,6-difluorophenyl)-6-methyl-5-phenyl-pyridazine-3-carbonitrile+TX,(R)-3-(difluoromethyl)-1-methyl-N-[1,1,3-trimethylindan-4-yl]pyrazole-4-carboxamide+TX,4-(2-bromo-4-fluoro-phenyl)-N-(2-chloro-6-fluoro-phenyl)-2,5-dimethyl-pyrazol-3-amine+TX,4-(2-bromo-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine+TX, fluindapyr+TX, coumethoxystrobin(jiaxiangjunzhi)+TX, Ivbenmixianan+TX, dichlobentiazox+TX,mandestrobin+TX,3-(4,4-difluoro-3,4-dihydro-3,3-dimethylisoquinolin-1-yl)quinolone+TX,2-[2-fluoro-6-[(8-fluoro-2-methyl-3-quinolyl)oxy]phenyl]propan-2-ol+TX,oxathiapiprolin+TX, tert-butylN-[6-[[[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamate+TX,pyraziflumid+TX, inpyrfluxam+TX, trolprocarb+TX, mefentrifluconazole+TX,ipfentrifluconazole+TX,2-(difluoromethyl)-N-[(3R)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide+TX,N′-(2,5-dimethyl-4-phenoxy-phenyl)-N-ethyl-N-methyl-formamidine+TX,N′-[4-(4,5-dichlorothiazol-2-yl)oxy-2,5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidine+TX,[2-[3-[2-[1-[2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-4-piperidyl]thiazol-4-yl]-4,5-dihydroisoxazol-5-yl]-3-chloro-phenyl]methanesulfonate+TX, but-3-ynylN-[6-[[(Z)-[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamate+TX,methylN-[[5-[4-(2,4-dimethylphenyl)triazol-2-yl]-2-methyl-phenyl]methyl]carbamate+TX,3-chloro-6-methyl-5-phenyl-4-(2,4,6-trifluorophenyl)pyridazine+TX,pyridachlometyl+TX,3-(difluoromethyl)-1-methyl-N-[1,1,3-trimethylindan-4-yl]pyrazole-4-carboxamide+TX,1-[2-[[1-(4-chlorophenyl)pyrazol-3-yl]oxymethyl]-3-methyl-phenyl]-4-methyl-tetrazol-5-one+TX,1-methyl-4-[3-methyl-2-[[2-methyl-4-(3,4,5-trimethylpyrazol-1-yl)phenoxy]methyl]phenyl]tetrazol-5-one+TX,aminopyrifen+TX, ametoctradin+TX, amisulbrom+TX, penflufen+TX,(Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide+TX,florylpicoxamid+TX, fenpicoxamid+TX, tebufloquin+TX, ipflufenoquin+TX,quinofumelin+TX, isofetamid+TX,N-[2-[2,4-dichloro-phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide+TX,N-[2-[2-chloro-4-(trifluoromethyl)phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide+TX,benzothiostrobin+TX, phenamacril+TX, 5-amino-1,3,4-thiadiazole-2-thiolzinc salt (2:1)+TX, fluopyram+TX, flutianil+TX, fluopimomide+TX,pyrapropoyne+TX, picarbutrazox+TX,2-(difluoromethyl)-N-(3-ethyl-1,1-dimethyl-indan-4-yl)pyridine-3-carboxamide+TX,2-(difluoromethyl)-N-((3R)-1, 1, 3-trimethylindan-4-yl)pyridine-3-carboxamide+TX,4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile+TX,metyltetraprole+TX, 2-(difluoromethyl)-N-((3R)-1, 1,3-trimethylindan-4-yl) pyridine-3-carboxamide+TX, α-(1,1-dimethylethyl)-α-[4′-(trifluoromethoxy) [1,1′-biphenyl]-4-yl]-5-pyrimidinemethanol+TX, fluoxapiprolin+TX,enoxastrobin+TX,4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile+TX,4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-sulfanyl-1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile+TX,4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-thioxo-4H-1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile+TX,trinexapac+TX, coumoxystrobin+TX, zhongshengmycin+TX, thiodiazolecopper+TX, zinc thiazole+TX, amectotractin+TX, iprodione+TX,N-octyl-N′-[2-(octylamino)ethyl]ethane-1,2-diamine+TX;N′-[5-bromo-2-methyl-6-[(1S)-1-methyl-2-propoxy-ethoxy]-3-pyridyl]-N-ethyl-N-methyl-formamidine+TX,N′-[5-bromo-2-methyl-6-[(1R)-1-methyl-2-propoxy-ethoxy]-3-pyridyl]-N-ethyl-N-methyl-formamidine+TX,N′-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine+TX,N′-[5-chloro-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine+TX,N′-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-isopropyl-N-methyl-formamidine+TX(these compounds may be prepared from the methods described inWO2015/155075);N′-[5-bromo-2-methyl-6-(2-propoxypropoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine+TX(this compound may be prepared from the methods described inIPCOM000249876D);N-isopropyl-N′-[5-methoxy-2-methyl-4-(2,2,2-trifluoro-1-hydroxy-1-phenyl-ethyl)phenyl]-N-methyl-formamidine+TX,N′-[4-(1-cyclopropyl-2,2,2-trifluoro-1-hydroxy-ethyl)-5-methoxy-2-methyl-phenyl]-N-isopropyl-N-methyl-formamidine+TX(these compounds may be prepared from the methods described inWO2018/228896);N-ethyl-N′-[5-methoxy-2-methyl-4-[(2-trifluoromethyl)oxetan-2-yl]phenyl]-N-methyl-formamidine+TX,N-ethyl-N′-[5-methoxy-2-methyl-4-[(2-trifuoromethyl)tetrahydrofuran-2-yl]phenyl]-N-methyl-formamidine+TX(these compounds may be prepared from the methods described inWO2019/110427);N-[(1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide+TX,N-[(1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide+TX,N-[(1R)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide+TX,N-[(1S)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide+TX,N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide+TX,N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide+TX,8-fluoro-N-[(1R)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide+TX,8-fluoro-N-[(1S)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide+TX,N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide+TX,N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide+TX,N-((1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide+TX,N-((1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide+TX(these compounds may be prepared from the methods described inWO2017/153380);

1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline+TX,1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,6-trifluoro-3,3-dimethyl-isoquinoline+TX,4,4-difluoro-3,3-dimethyl-1-(6-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline+TX,4,4-difluoro-3,3-dimethyl-1-(7-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline+TX,1-(6-chloro-7-methyl-pyrazolo[1,5-a]pyridin-3-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline+TX(these compounds may be prepared from the methods described inWO2017/025510);1-(4,5-dimethylbenzimidazol-1-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline+TX,1-(4,5-dimethylbenzimidazol-1-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline+TX,6-chloro-4,4-difluoro-3,3-dimethyl-1-(4-methylbenzimidazol-1-yl)isoquinoline+TX,4,4-difluoro-1-(5-fluoro-4-methyl-benzimidazol-1-yl)-3,3-dimethyl-isoquinoline+TX,3-(4,4-difluoro-3,3-dimethyl-1-isoquinolyl)-7,8-dihydro-6H-cyclopenta[e]benzimidazole+TX(these compounds may be prepared from the methods described inWO2016/156085);N-methoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]cyclopropanecarboxamide+TX,N,2-dimethoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide+TX,N-ethyl-2-methyl-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide+TX,1-methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea+TX,1,3-dimethoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea+TX,3-ethyl-1-methoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea+TX,N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide+TX,4,4-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one+TX,5,5-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one+TX,ethyl1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]pyrazole-4-carboxylate+TX,N,N-dimethyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-1,2,4-triazol-3-amine+TX.The compounds in this paragraph may be prepared from the methodsdescribed in WO 2017/055473, WO 2017/055469, WO 2017/093348 and WO2017/118689;2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol+TX(this compound may be prepared from the methods described in WO2017/029179);2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol+TX(this compound may be prepared from the methods described in WO2017/029179);3-[2-(1-chlorocyclopropyl)-3-(2-fluorophenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile+TX(this compound may be prepared from the methods described in WO2016/156290);3-[2-(1-chlorocyclopropyl)-3-(3-chloro-2-fluoro-phenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile+TX(this compound may be prepared from the methods described in WO2016/156290); (4-phenoxyphenyl)methyl2-amino-6-methyl-pyridine-3-carboxylate+TX (this compound may beprepared from the methods described in WO 2014/006945);2,6-Dimethyl-1H,5H-[1,4]dithiino[2,3-c:5,6-c′]dipyrrole-1,3,5,7(2H,6H)-tetrone+TX(this compound may be prepared from the methods described in WO2011/138281);N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzenecarbothioamide+TX;N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide+TX;(Z,2E)-5-[1-(2,4-dichlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide+TX(this compound may be prepared from the methods described in WO2018/153707);N′-(2-chloro-5-methyl-4-phenoxy-phenyl)-N-ethyl-N-methyl-formamidine+TX;N′-[2-chloro-4-(2-fluorophenoxy)-5-methyl-phenyl]-N-ethyl-N-methyl-formamidine+TX(this compound may be prepared from the methods described in WO2016/202742);2-(difluoromethyl)-N-[(3S)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide+TX(this compound may be prepared from the methods described in WO2014/095675);(5-methyl-2-pyridyl)-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone+TX,(3-methylisoxazol-5-yl)-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone+TX(these compounds may be prepared from the methods described in WO2017/220485);2-oxo-N-propyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide+TX(this compound may be prepared from the methods described in WO2018/065414); ethyl1-[[5-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-2-thienyl]methyl]pyrazole-4-carboxylate+TX(this compound may be prepared from the methods described in WO2018/158365);2,2-difluoro-N-methyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide+TX,N-[(E)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide+TX,N—[(Z)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide+TX,N—[N-methoxy-C-methyl-carbonimidoyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide+TX(these compounds may be prepared from the methods described in WO2018/202428); microbials including: Acinetobacter Iwoffii+TX, Acremoniumalternatum+TX+TX, Acremonium cephalosporium+TX+TX, Acremoniumdiospyri+TX, Acremonium obclavatum+TX, Adoxophyes orana granulovirus(AdoxGV) (Capex®)+TX, Agrobacterium radiobacter strain K84(Galltrol-A®)+TX, Alternaria alternate+TX, Alternaria cassia+TX,Alternaria destruens (Smolder®)+TX, Ampelomyces quisqualis (AQ10®)+TX,Aspergillus flavus AF36 (AF36®)+TX, Aspergillus flavus NRRL 21882(Aflaguard®)+TX, Aspergillus spp.+TX, Aureobasidium pullulans+TX,Azospirillum+TX, (MicroAZ®+TX, TAZO B®)+TX, Azotobacter+TX, Azotobacterchroocuccum (Azotomeal®)+TX, Azotobacter cysts (Bionatural BloomingBlossoms®)+TX, Bacillus amyloliquefaciens+TX, Bacillus cereus+TX,Bacillus chitinosporus strain CM-1+TX, Bacillus chitinosporus strainAQ746+TX, Bacillus licheniformis strain HB-2 (Biostart™ Rhizoboost®)+TX,Bacillus licheniformis strain 3086 (EcoGuard®+TX, Green Releaf®)+TX,Bacillus circulans+TX, Bacillus firmus (BioSafe®+TX, BioNem-WP®+TX,VOTiVO®)+TX, Bacillus firmus strain 1-1582+TX, Bacillus macerans+TX,Bacillus marismortui+TX, Bacillus megaterium+TX, Bacillus mycoidesstrain AQ726+TX, Bacillus papillae (Milky Spore Powder®)+TX, Bacilluspumilus spp.+TX, Bacillus pumilus strain GB34 (Yield Shield®)+TX,Bacillus pumilus strain AQ717+TX, Bacillus pumilus strain QST 2808(Sonata®+TX, Ballad Plus®)+TX, Bacillus spahericus (VectoLex®)+TX,Bacillus spp.+TX, Bacillus spp. strain AQ175+TX, Bacillus spp. strainAQ177+TX, Bacillus spp. strain AQ178+TX, Bacillus subtilis strain QST713 (CEASE®+TX, Serenade®+TX, Rhapsody®)+TX, Bacillus subtilis strainQST 714 (JAZZ®)+TX, Bacillus subtilis strain AQ153+TX, Bacillus subtilisstrain AQ743+TX, Bacillus subtilis strain QST3002+TX, Bacillus subtilisstrain QST3004+TX, Bacillus subtilis var. amyloliquefaciens strain FZB24(Taegro®+TX, Rhizopro®)+TX, Bacillus thuringiensis Cry 2Ae+TX, Bacillusthuringiensis Cry1 Ab+TX, Bacillus thuringiensis aizawai GC 91(Agree®)+TX, Bacillus thuringiensis israelensis (BMP123®+TX,Aquabac®+TX, VectoBac®)+TX, Bacillus thuringiensis kurstaki(Javelin®+TX, Deliver®+TX, CryMax®+TX, Bonide®+TX, Scutella WP®+TX,Turilav WP®+TX, Astuto®+TX, Dipel WP®+TX, Biobit®+TX, Foray®)+TX,Bacillus thuringiensis kurstaki BMP 123 (Baritone®)+TX, Bacillusthuringiensis kurstaki HD-1 (Bioprotec-CAF/3P®)+TX, Bacillusthuringiensis strain BD #32+TX, Bacillus thuringiensis strain AQ52+TX,Bacillus thuringiensis var. aizawai (XenTari®+TX, DiPel®)+TX, bacteriaspp. (GROWMEND®+TX, GROWSWEET®+TX, Shootup®)+TX, bacteriophage ofClavipacter michiganensis (AgriPhage®)+TX, Bakflor®+TX, Beauveriabassiana (Beaugenic®+TX, Brocaril WP®)+TX, Beauveria bassiana GHA(Mycotrol ES®+TX, Mycotrol O®+TX, BotaniGuard®)+TX, Beauveriabrongniartii (Engerlingspilz®+TX, Schweizer Beauveria®+TX,Melocont®)+TX, Beauveria spp.+TX, Botrytis cineria+TX, Bradyrhizobiumjaponicum (TerraMax®)+TX, Brevibacillus brevis+TX, Bacillusthuringiensis tenebrionis (Novodor®)+TX, BtBooster+TX, Burkholderiacepacia (Deny®+TX, Intercept®+TX, Blue Circle®)+TX, Burkholderiagladii+TX, Burkholderia gladioli+TX, Burkholderia spp.+TX, Canadianthistle fungus (CBH Canadian Bioherbicide®)+TX, Candida butyri+TX,Candida famata+TX, Candida fructus+TX, Candida glabrata+TX, Candidaguilliermondii+TX, Candida melibiosica+TX, Candida oleophila strainO+TX, Candida parapsilosis+TX, Candida pelliculosa+TX, Candidapulcherrima+TX, Candida reukaufii+TX, Candida saitoana (Bio-Coat®+TX,Biocure®)+TX, Candida sake+TX, Candida spp.+TX, Candida tenius+TX,Cedecea dravisae+TX, Cellulomonas flavigena+TX, Chaetomium cochliodes(Nova-Cide®)+TX, Chaetomium globosum (Nova-Cide®)+TX, Chromobacteriumsubtsugae strain PRAA4-1T (Grandevo®)+TX, Cladosporiumcladosporioides+TX, Cladosporium oxysporum+TX, Cladosporiumchlorocephalum+TX, Cladosporium spp.+TX, Cladosporium tenuissimum+TX,Clonostachys rosea (EndoFine®)+TX, Colletotrichum acutatum+TX,Coniothyrium minitans (Cotans WG®)+TX, Coniothyrium spp.+TX,Cryptococcus albidus (YIELDPLUS®)+TX, Cryptococcus humicola+TX,Cryptococcus infirmominiatus+TX, Cryptococcus laurentii+TX,Cryptophlebia leucotreta granulovirus (Cryptex®)+TX, Cupriaviduscampinensis+TX, Cydia pomonella granulovirus (CYD-X®)+TX, Cydiapomonella granulovirus (Madex®+TX, Madex Plus®+TX, MadexMax/Carpovirusine®)+TX, Cylindrobasidium laeve (Stumpout®)+TX,Cylindrocladium+TX, Debaryomyces hansenii+TX, Drechslerahawaiinensis+TX, Enterobacter cloacae+TX, Enterobacteriaceae+TX,Entomophtora virulenta (Vektor®)+TX, Epicoccum nigrum+TX, Epicoccumpurpurascens+TX, Epicoccum spp.+TX, Filobasidium floriforme+TX, Fusariumacuminatum+TX, Fusarium chlamydosporum+TX, Fusarium oxysporum(Fusaclean®/Biofox C®)+TX, Fusarium proliferatum+TX, Fusarium spp.+TX,Galactomyces geotrichum+TX, Gliocladium catenulatum (Primastop®+TX,Prestop®)+TX, Gliocladium roseum+TX, Gliocladium spp. (SoilGard®)+TX,Gliocladium virens (Soilgard®)+TX, Granulovirus (Granupom®)+TX,Halobacillus halophilus+TX, Halobacillus litoralis+TX, Halobacillustrueperi+TX, Halomonas spp.+TX, Halomonas subglaciescola+TX, Halovibriovariabilis+TX, Hanseniaspora uvarum+TX, Helicoverpa armigeranucleopolyhedrovirus (Helicovex®)+TX, Helicoverpa zea nuclearpolyhedrosis virus (Gemstar®)+TX, Isoflavone—formononetin(Myconate®)+TX, Kloeckera apiculata+TX, Kloeckera spp.+TX, Lagenidiumgiganteum (Laginex®)+TX, Lecanicillium longisporum (Vertiblast®)+TX,Lecanicillium muscarium (Vertikil®)+TX, Lymantria Disparnucleopolyhedrosis virus (Disparvirus®)+TX, Marinococcus halophilus+TX,Meira geulakonigii+TX, Metarhizium anisopliae (Met52®)+TX, Metarhiziumanisopliae (Destruxin WP®)+TX, Metschnikowia fruticola (Shemer®)+TX,Metschnikowia pulcherrima+TX, Microdochium dimerum (Antibot®)+TX,Micromonospora coerulea+TX, Microsphaeropsis ochracea+TX, Muscodor albus620 (Muscudor®)+TX, Muscodor roseus strain A₃-5+TX, Mycorrhizae spp.(AMykor®+TX, Root Maximizer®)+TX, Myrothecium verrucaria strainAARC-0255 (DiTera®)+TX, BROS PLUS®+TX, Ophiostoma piliferum strain D97(Sylvanex®)+TX, Paecilomyces farinosus+TX, Paecilomyces fumosoroseus(PFR-97®+TX, PreFeRal®)+TX, Paecilomyces linacinus (Biostat WP®)+TX,Paecilomyces lilacinus strain 251 (MeloCon WG®)+TX, Paenibacilluspolymyxa+TX, Pantoea agglomerans (BlightBan C9-1®)+TX, Pantoea spp.+TX,Pasteuria spp. (Econem®)+TX, Pasteuria nishizawae+TX, Penicilliumaurantiogriseum+TX, Penicillium billai (Jumpstart®+TX, TagTeam®)+TX,Penicillium brevicompactum+TX, Penicillium frequentans+TX, Penicilliumgriseofulvum+TX, Penicillium purpurogenum+TX, Penicillium spp.+TX,Penicillium viridicatum+TX, Phlebiopsis gigantean (Rotstop®)+TX,phosphate solubilizing bacteria (Phosphomeal®)+TX, Phytophthoracryptogea+TX, Phytophthora palmivora (Devine®)+TX, Pichia anomala+TX,Pichia guilermondii+TX, Pichia membranaefaciens+TX, Pichia onychis+TX,Pichia stipites+TX, Pseudomonas aeruginosa+TX, Pseudomonas aureofasciens(Spot-Less Biofungicide®)+TX, Pseudomonas cepacia+TX, Pseudomonaschlororaphis (AtEze®)+TX, Pseudomonas corrugate+TX, Pseudomonasfluorescens strain A506 (BlightBan A506®)+TX, Pseudomonas putida+TX,Pseudomonas reactans+TX, Pseudomonas spp.+TX, Pseudomonas syringae(Bio-Save®)+TX, Pseudomonas viridiflava+TX, Pseudomons fluorescens(Zequanox®)+TX, Pseudozyma flocculosa strain PF-A22 UL (Sporodex L®)+TX,Puccinia canaliculata+TX, Puccinia thlaspeos (Wood Warrior®)+TX, Pythiumparoecandrum+TX, Pythium oligandrum (Polygandron®+TX, Polyversum®)+TX,Pythium periplocum+TX, Rhanella aquatilis+TX, Rhanella spp.+TX, Rhizobia(Dormal®+TX, Vault®)+TX, Rhizoctonia+TX, Rhodococcus globerulus strainAQ719+TX, Rhodosporidium diobovatum+TX, Rhodosporidium toruloides+TX,Rhodotorula spp.+TX, Rhodotorula glutinis+TX, Rhodotorula graminis+TX,Rhodotorula mucilagnosa+TX, Rhodotorula rubra+TX, Saccharomycescerevisiae+TX, Salinococcus roseus+TX, Sclerotinia minor+TX, Sclerotiniaminor (SARRITOR®)+TX, Scytalidium spp.+TX, Scytalidium uredinicola+TX,Spodoptera exigua nuclear polyhedrosis virus (Spod-X®+TX, Spexit®)+TX,Serratia marcescens+TX, Serratia plymuthica+TX, Serratia spp.+TX,Sordaria fimicola+TX, Spodoptera littoralis nucleopolyhedrovirus(Littovir®)+TX, Sporobolomyces roseus+TX, Stenotrophomonasmaltophilia+TX, Streptomyces ahygroscopicus+TX, Streptomycesalbaduncus+TX, Streptomyces exfoliates+TX, Streptomyces galbus+TX,Streptomyces griseoplanus+TX, Streptomyces griseoviridis (Mycostop®)+TX,Streptomyces lydicus (Actinovate®)+TX, Streptomyces lydicus WYEC-108(ActinoGrow®)+TX, Streptomyces violaceus+TX, Tilletiopsis minor+TX,Tilletiopsis spp.+TX, Trichoderma asperellum (T34 Biocontrol®)+TX,Trichoderma gamsii (Tenet®)+TX, Trichoderma atroviride (Plantmate®)+TX,Trichoderma hamatum TH 382+TX, Trichoderma harzianum rifai(Mycostar®)+TX, Trichoderma harzianum T-22 (Trianum-P®+TX, PlantShieldHCO+TX, RootShield®+TX, Trianum-G®)+TX, Trichoderma harzianum T-39(Trichodex®)+TX, Trichoderma inhamatum+TX, Trichoderma koningii+TX,Trichoderma spp. LC 52 (Sentinel®)+TX, Trichoderma lignorum+TX,Trichoderma longibrachiatum+TX, Trichoderma polysporum (Binab T®)+TX,Trichoderma taxi+TX, Trichoderma virens+TX, Trichoderma virens (formerlyGliocladium virens GL-21) (SoilGuard®)+TX, Trichoderma viride+TX,Trichoderma viride strain ICC 080 (Remedier®)+TX, Trichosporonpullulans+TX, Trichosporon spp.+TX, Trichothecium spp.+TX, Trichotheciumroseum+TX, Typhula phacorrhiza strain 94670+TX, Typhula phacorrhizastrain 94671+TX, Ulocladium atrum+TX, Ulocladium oudemansii(Botry-Zen®)+TX, Ustilago maydis+TX, various bacteria and supplementarymicronutrients (Natural II®)+TX, various fungi (MillenniumMicrobes®)+TX, Verticillium chlamydosporium+TX, Verticillium lecanii(Mycotal®+TX, Vertalec®)+TX, Vip3Aa20 (VIPtera®)+TX, Virgibaclillusmarismortui+TX, Xanthomonas campestris pv. Poae (Camperico®)+TX,Xenorhabdus bovienii+TX, Xenorhabdus nematophilus;

Plant extracts including: pine oil (Retenol®)+TX, azadirachtin (PlasmaNeem Oil®+TX, AzaGuard®+TX, MeemAzal®+TX, Molt-X®+TX, Botanical IGR(Neemazad®+TX, Neemix®)+TX, canola oil (Lilly Miller Vegol®)+TX,Chenopodium ambrosioides near ambrosioides (Requiem®)+TX, Chrysanthemumextract (Crisant®)+TX, extract of neem oil (Trilogy®)+TX, essentialsoils of Labiatae (Botania®)+TX, extracts of clove rosemary peppermintand thyme oil (Garden insect Killer®)+TX, Glycinebetaine(Greenstim®)+TX, garlic+TX, lemongrass oil (GreenMatch®)+TX, neemoil+TX, Nepeta cataria (Catnip oil)+TX, Nepeta catarina+TX, nicotine+TX,oregano oil (MossBuster®)+TX, Pedaliaceae oil (Nematon®)+TX,pyrethrum+TX, Quillaja saponaria (NemaQ®)+TX, Reynoutria sachalinensis(Regalia®+TX, Sakalia®)+TX, rotenone (Eco Roten®)+TX, Rutaceae plantextract (Soleo®)+TX, soybean oil (Ortho Ecosense®)+TX, tea tree oil(Timorex Gold®)+TX, thymus oil+TX, AGNIQUE® MMF+TX, BugOil®+TX, mixtureof rosemary sesame pepermint thyme and cinnamon extracts (EF 300®)+TX,mixture of clove rosemary and peppermint extract (EF 400®)+TX, mixtureof clove pepermint garlic oil and mint (Soil Shot®)+TX, kaolin(Screen®)+TX, storage glucam of brown algae (Laminarin®);

pheromones including: blackheaded fireworm pheromone (3M SprayableBlackheaded Fireworm Pheromone®)+TX, Codling Moth Pheromone (Paramountdispenser-(CM)/Isomate C-Plus®)+TX, Grape Berry Moth Pheromone (3MMEC-GBM Sprayable Pheromone®)+TX, Leafroller pheromone (3M MEC-LRSprayable Pheromone®)+TX, Muscamone (Snip7 Fly Bait®+TX, Starbar PremiumFly Bait®)+TX, Oriental Fruit Moth Pheromone (3M oriental fruit mothsprayable Pheromone®)+TX, Peachtree Borer Pheromone (Isomate-P®)+TX,Tomato Pinworm Pheromone (3M Sprayable Pheromone®)+TX, Entostat powder(extract from palm tree) (Exosex CM®)+TX, (E+TX,Z+TX,Z)-3+TX,8+TX,11Tetradecatrienyl acetate+TX,(Z+TX,Z+TX,E)-7+TX,11+TX,13-Hexadecatrienal+TX,(E+TX,Z)-7+TX,9-Dodecadien-1-yl acetate+TX, 2-Methyl-1-butanol+TX,Calcium acetate+TX, Scenturion®+TX, Biolure®+TX, Check-Mate®+TX,Lavandulyl senecioate; Macrobials including: Aphelinus abdominalis+TX,Aphidius ervi (Aphelinus-System®)+TX, Acerophagus papaya+TX, Adaliabipunctata (Adalia-System®)+TX, Adalia bipunctata (Adaline®)+TX, Adaliabipunctata (Aphidalia®)+TX, Ageniaspis citricola+TX, Ageniaspisfuscicollis+TX, Amblyseius andersoni (Anderline®+TX,Andersoni-System®)+TX, Amblyseius californicus (Amblyline®+TX,Spical®)+TX, Amblyseius cucumeris (Thripex®+TX, Bugline Cucumeris®)+TX,Amblyseius fallacis (Fallacis®)+TX, Amblyseius swirskii (BuglineSwirskii®+TX, Swirskii-Mite®)+TX, Amblyseius womersleyi (WomerMite®)+TX,Amitus hesperidum+TX, Anagrus atomus+TX, Anagyrus fusciventris+TX,Anagyrus kamali+TX, Anagyrus loecki+TX, Anagyrus pseudococci(Citripar®)+TX, Anicetus benefices+TX, Anisopteromalus calandrae+TX,Anthocoris nemoralis (Anthocoris-System®)+TX, Aphelinus abdominalis(Apheline®+TX, Aphiline®)+TX, Aphelinus asychis+TX, Aphidius colemani(Aphipar®)+TX, Aphidius ervi (Ervipar®)+TX, Aphidius gifuensis+TX,Aphidius matricariae (Aphipar-M®)+TX, Aphidoletes aphidimyza(Aphidend®)+TX, Aphidoletes aphidimyza (Aphidoline®)+TX, Aphytislingnanensis+TX, Aphytis melinus+TX, Aprostocetus hagenowii+TX, Athetacoriaria (Staphyline®)+TX, Bombus spp.+TX, Bombus terrestris (NatupolBeehive®)+TX, Bombus terrestris (Beeline®+TX, Tripol®)+TX, Cephalonomiastephanoderis+TX, Chilocorus nigritus+TX, Chrysoperla carnea(Chrysoline®)+TX, Chrysoperla carnea (Chrysopa®)+TX, Chrysoperlarufilabris+TX, Cirrospilus ingenuus+TX, Cirrospilus quadristriatus+TX,Citrostichus phyllocnistoides+TX, Closterocerus chamaeleon+TX,Closterocerus spp.+TX, Coccidoxenoides perminutus (Planopar®)+TX,Coccophagus cowperi+TX, Coccophagus lycimnia+TX, Cotesia flavipes+TX,Cotesia plutellae+TX, Cryptolaemus montrouzieri (Cryptobug®+TX,Cryptoline®)+TX, Cybocephalus nipponicus+TX, Dacnusa sibirica+TX,Dacnusa sibirica (Minusa®)+TX, Diglyphus isaea (Diminex®)+TX, Delphastuscatalinae (Delphastus®)+TX, Delphastus pusillus+TX, Diachasmimorphakrausii+TX, Diachasmimorpha longicaudata+TX, Diaparsis jucunda+TX,Diaphorencyrtus aligarhensis+TX, Diglyphus isaea+TX, Diglyphus isaea(Miglyphus®+TX, Digline®)+TX, Dacnusa sibirica (DacDigline®+TX,Minex®)+TX, Diversinervus spp.+TX, Encarsia citrina+TX, Encarsia formosa(Encarsia Max®+TX, Encarline®+TX, En-Strip®)+TX, Eretmocerus eremicus(Enermix®)+TX, Encarsia guadeloupae+TX, Encarsia haitiensis+TX,Episyrphus balteatus (Syrphidend®)+TX, Eretmoceris siphonini+TX,Eretmocerus californicus+TX, Eretmocerus eremicus (Ercal®+TX, Eretlinee®)+TX, Eretmocerus eremicus (Bemimix®)+TX, Eretmocerus hayati+TX,Eretmocerus mundus (Bemipar®+TX, Eretline m®)+TX, Eretmocerussiphonini+TX, Exochomus quadripustulatus+TX, Feltiella acarisuga(Spidend®)+TX, Feltiella acarisuga (Feltiline®)+TX, Fopius arisanus+TX,Fopius ceratitivorus+TX, Formononetin (Wirless Beehome®)+TX,Franklinothrips vespiformis (Vespop®)+TX, Galendromus occidentalis+TX,Goniozus legneri+TX, Habrobracon hebetor+TX, Harmonia axyridis(HarmoBeetle®)+TX, Heterorhabditis spp. (Lawn Patrol®)+TX,Heterorhabditis bacteriophora (NemaShield HB®+TX, Nemaseek®+TX,Terranem-Nam®+TX, Terranem®+TX, Larvanem®+TX, B-Green®+TX,NemAttack®+TX, Nematop®)+TX, Heterorhabditis megidis (Nemasys H®+TX,BioNem H®+TX, Exhibitline hm®+TX, Larvanem-M®)+TX, Hippodamiaconvergens+TX, Hypoaspis aculeifer (Aculeifer-System®+TX,Entomite-A®)+TX, Hypoaspis miles (Hypoline m®+TX, Entomite-M®)+TX,Lbalia leucospoides+TX, Lecanoideus floccissimus+TX, Lemophaguserrabundus+TX, Leptomastidea abnormis+TX, Leptomastix dactylopii(Leptopar®)+TX, Leptomastix epona+TX, Lindorus lophanthae+TX, Lipolexisoregmae+TX, Lucilia caesar (Natufly®)+TX, Lysiphlebus testaceipes+TX,Macrolophus caliginosus (Mirical-N®+TX, Macroline c®+TX, Mirical®)+TX,Mesoseiulus longipes+TX, Metaphycus flavus+TX, Metaphycus lounsburyi+TX,Micromus angulatus (Milacewing®)+TX, Microterys flavus+TX, Muscidifuraxraptorellus and Spalangia cameroni (Biopar®)+TX, Neodryinustyphlocybae+TX, Neoseiulus californicus+TX, Neoseiulus cucumeris(THRYPEX®)+TX, Neoseiulus fallacis+TX, Nesideocoris tenuis(NesidioBug®+TX, Nesibug®)+TX, Ophyra aenescens (Biofly®)+TX, Oriusinsidiosus (Thripor-I®+TX, Oriline i®)+TX, Orius laevigatus(Thripor-L®+TX, Oriline I®)+TX, Orius majusculus (Oriline m®)+TX, Oriusstrigicollis (Thripor-S®)+TX, Pauesia juniperorum+TX, Pediobiusfoveolatus+TX, Phasmarhabditis hermaphrodita (Nemaslug®)+TX,Phymastichus coffea+TX, Phytoseiulus macropilus+TX, Phytoseiuluspersimilis (Spidex®+TX, Phytoline p®)+TX, Podisus maculiventris(Podisus®)+TX, Pseudacteon curvatus+TX, Pseudacteon obtusus+TX,Pseudacteon tricuspis+TX, Pseudaphycus maculipennis+TX, Pseudleptomastixmexicana+TX, Psyllaephagus pilosus+TX, Psyttalia concolor (complex)+TX,Quadrastichus spp.+TX, Rhyzobius lophanthae+TX, Rodolia cardinalis+TX,Rumina decollate+TX, Semielacher petiolatus+TX, Sitobion avenae(Ervibank®)+TX, Steinernema carpocapsae (Nematac C®+TX, Millenium®+TX,BioNem C®+TX, NemAttack®+TX, Nemastar®+TX, Capsanem®)+TX, Steinernemafeltiae (NemaShield®+TX, Nemasys F®+TX, BioNem F®+TX,Steinernema-System®+TX, NemAttack®+TX, Nemaplus®+TX, Exhibitline sf®+TX,Scia-Rid®+TX, Entonem®)+TX, Steinernema kraussei (Nemasys L®+TX, BioNemL®+TX, Exhibitline srb®)+TX, Steinernema riobrave (BioVector®+TX,BioVektor®)+TX, Steinernema scapterisci (Nematac S®)+TX, Steinernemaspp.+TX, Steinernematid spp. (Guardian Nematodes®)+TX, Stethoruspunctillum (Stethorus®)+TX, Tamarixia radiate+TX, Tetrastichussetifer+TX, Thripobius semiluteus+TX, Torymus sinensis+TX, Trichogrammabrassicae (Tricholine b®)+TX, Trichogramma brassicae (Tricho-Strip®)+TX,Trichogramma evanescens+TX, Trichogramma minutum+TX, Trichogrammaostriniae+TX, Trichogramma platneri+TX, Trichogramma pretiosum+TX,Xanthopimpla stemmator; other biologicals including: abscisic acid+TX,bioSea®+TX, Chondrostereum purpureum (Chontrol Paste®)+TX,Colletotrichum gloeosporioides (Collego®)+TX, Copper Octanoate(Cueva®)+TX, Delta traps (Trapline d®)+TX, Erwinia amylovora (Harpin)(ProAct®+TX, Ni-HIBIT Gold CST®)+TX, Ferri-phosphate (Ferramol®)+TX,Funnel traps (Trapline y®)+TX, Gallex®+TX, Grower's Secret®+TX,Homo-brassonolide+TX, Iron Phosphate (Lilly Miller Worry Free FerramolSlug & Snail Bait®)+TX, MCP hail trap (Trapline f®)+TX, Microctonushyperodae+TX, Mycoleptodiscus terrestris (Des-X®)+TX, BioGain®+TX,Aminomite®+TX, Zenox®+TX, Pheromone trap (Thripline Ams®)+TX, potassiumbicarbonate (MilStop®)+TX, potassium salts of fatty acids (Sanova®)+TX,potassium silicate solution (Sil-Matrix®)+TX, potassiumiodide+potassiumthiocyanate (Enzicur®)+TX, SuffOil-X®+TX, Spidervenom+TX, Nosema locustae (Semaspore Organic Grasshopper Control®)+TX,Sticky traps (Trapline YF®+TX, Rebell Amarillo®)+TX and Traps(Takitrapline y+b®)+TX; and

a safener, such as benoxacor+TX, cloquintocet (includingcloquintocet-mexyl)+TX, cyprosulfamide+TX, dichlormid+TX, fenchlorazole(including fenchlorazole-ethyl)+TX, fenclorim+TX, fluxofenim+TX,furilazole+TX, isoxadifen (including isoxadifen-ethyl)+TX, mefenpyr(including mefenpyr-diethyl)+TX, metcamifen+TX and oxabetrinil+TX.

The references in brackets behind the active ingredients, e.g.[3878-19-1] refer to the Chemical Abstracts Registry number. The abovedescribed mixing partners are known. Where the active ingredients areincluded in “The Pesticide Manual” [The Pesticide Manual—A WorldCompendium; Thirteenth Edition; Editor: C. D. S. TomLin; The BritishCrop Protection Council], they are described therein under the entrynumber given in round brackets hereinabove for the particular compound;for example, the compound “abamectin” is described under entry number(1). Where “[CCN]” is added hereinabove to the particular compound, thecompound in question is included in the “Compendium of Pesticide CommonNames”, which is accessible on the internet [A. Wood; Compendium ofPesticide Common Names, Copyright © 1995-2004]; for example, thecompound “acetoprole” is described under the internet addresshttp://www.alanwood.net/pesticides/acetoprole.html.

Most of the active ingredients described above are referred tohereinabove by a so-called “common name”, the relevant “ISO common name”or another “common name” being used in individual cases. If thedesignation is not a “common name”, the nature of the designation usedinstead is given in round brackets for the particular compound; in thatcase, the IUPAC name, the IUPAC/Chemical Abstracts name, a “chemicalname”, a “traditional name”, a “compound name” or a “develoment code” isused or, if neither one of those designations nor a “common name” isused, an “alternative name” is employed. “CAS Reg. No” means theChemical Abstracts Registry Number.

The active ingredient mixture of the compounds of formula I selectedfrom the compounds defined in the Tables D-1 to D-66 and Table P withactive ingredients described above comprises a compound selected fromone compound defined in the Tables D-1 to D-66 and Table P and an activeingredient as described above preferably in a mixing ratio of from 100:1to 1:6000, especially from 50:1 to 1:50, more especially in a ratio offrom 20:1 to 1:20, even more especially from 10:1 to 1:10, veryespecially from 5:1 to 1:5, special preference being given to a ratio offrom 2:1 to 1:2, and a ratio of from 4:1 to 2:1 being likewisepreferred, above all in a ratio of 1:1, or 5:1, or 5:2, or 5:3, or 5:4,or 4:1, or 4:2, or 4:3, or 3:1, or 3:2, or 2:1, or 1:5, or 2:5, or 3:5,or 4:5, or 1:4, or 2:4, or 3:4, or 1:3, or 2:3, or 1:2, or 1:600, or1:300, or 1:150, or 1:35, or 2:35, or 4:35, or 1:75, or 2:75, or 4:75,or 1:6000, or 1:3000, or 1:1500, or 1:350, or 2:350, or 4:350, or 1:750,or 2:750, or 4:750. Those mixing ratios are by weight.

The compounds and mixtures as described above can be used in a methodfor controlling pests, which comprises applying a composition comprisinga compound or mixture respectively as described above to the pests ortheir environment, with the exception of a method for treatment of thehuman or animal body by surgery or therapy and diagnostic methodspractised on the human or animal body.

The mixtures comprising a compound of formula I selected from thecompounds defined in the Tables D-1 to D-66 and Table P and one or moreactive ingredients as described above can be applied, for example, in asingle “ready-mix” form, in a combined spray mixture composed fromseparate formulations of the single active ingredient components, suchas a “tank-mix”, and in a combined use of the single active ingredientswhen applied in a sequential manner, i.e. one after the other with areasonably short period, such as a few hours or days. The order ofapplying the compounds of formula I and the active ingredients asdescribed above is not essential for working the present invention.

The compositions according to the invention can also comprise furthersolid or liquid auxiliaries, such as stabilizers, for exampleunepoxidized or epoxidized vegetable oils (for example epoxidizedcoconut oil, rapeseed oil or soya oil), antifoams, for example siliconeoil, preservatives, viscosity regulators, binders and/or tackifiers,fertilizers or other active ingredients for achieving specific effects,for example bactericides, fungicides, nematocides, plant activators,molluscicides or herbicides.

The compositions according to the invention are prepared in a mannerknown per se, in the absence of auxiliaries for example by grinding,screening and/or compressing a solid active ingredient and in thepresence of at least one auxiliary for example by intimately mixingand/or grinding the active ingredient with the auxiliary (auxiliaries).These processes for the preparation of the compositions and the use ofthe compounds I for the preparation of these compositions are also asubject of the invention.

The application methods for the compositions, that is the methods ofcontrolling pests of the abovementioned type, such as spraying,atomizing, dusting, brushing on, dressing, scattering or pouring—whichare to be selected to suit the intended aims of the prevailingcircumstances—and the use of the compositions for controlling pests ofthe abovementioned type are other subjects of the invention. Typicalrates of concentration are between 0.1 and 1000 ppm, preferably between0.1 and 500 ppm, of active ingredient. The rate of application perhectare is generally 1 to 2000 g of active ingredient per hectare, inparticular 10 to 1000 g/ha, preferably 10 to 600 g/ha.

A preferred method of application in the field of crop protection isapplication to the foliage of the plants (foliar application), it beingpossible to select frequency and rate of application to match the dangerof infestation with the pest in question. Alternatively, the activeingredient can reach the plants via the root system (systemic action),by drenching the locus of the plants with a liquid composition or byincorporating the active ingredient in solid form into the locus of theplants, for example into the soil, for example in the form of granules(soil application). In the case of paddy rice crops, such granules canbe metered into the flooded paddy-field.

The compounds of formula I of the invention and compositions thereof arealso be suitable for the protection of plant propagation material, forexample seeds, such as fruit, tubers or kernels, or nursery plants,against pests of the abovementioned type. The propagation material canbe treated with the compound prior to planting, for example seed can betreated prior to sowing. Alternatively, the compound can be applied toseed kernels (coating), either by soaking the kernels in a liquidcomposition or by applying a layer of a solid composition. It is alsopossible to apply the compositions when the propagation material isplanted to the site of application, for example into the seed furrowduring drilling. These treatment methods for plant propagation materialand the plant propagation material thus treated are further subjects ofthe invention. Typical treatment rates would depend on the plant andpest/fungi to be controlled and are generally between 1 to 200 grams per100 kg of seeds, preferably between 5 to 150 grams per 100 kg of seeds,such as between 10 to 100 grams per 100 kg of seeds.

The term seed embraces seeds and plant propagules of all kinds includingbut not limited to true seeds, seed pieces, suckers, corns, bulbs,fruit, tubers, grains, rhizomes, cuttings, cut shoots and the like andmeans in a preferred embodiment true seeds.

The present invention also comprises seeds coated or treated with orcontaining a compound of formula I. The term “coated or treated withand/or containing” generally signifies that the active ingredient is forthe most part on the surface of the seed at the time of application,although a greater or lesser part of the ingredient may penetrate intothe seed material, depending on the method of application. When the saidseed product is (re)planted, it may absorb the active ingredient. In anembodiment, the present invention makes available a plant propagationmaterial adhered thereto with a compound of formula I. Further, it ishereby made available, a composition comprising a plant propagationmaterial treated with a compound of formula I.

Seed treatment comprises all suitable seed treatment techniques known inthe art, such as seed dressing, seed coating, seed dusting, seed soakingand seed pelleting. The seed treatment application of the compoundformula I can be carried out by any known methods, such as spraying orby dusting the seeds before sowing or during the sowing/planting of theseeds.

The compounds of the invention can be distinguished from other similarcompounds by virtue of greater efficacy at low application rates and/ordifferent pest control, which can be verified by the person skilled inthe art using the experimental procedures, using lower concentrations ifnecessary, for example 10 ppm, 5 ppm, 2 ppm, 1 ppm or 0.2 ppm; or lowerapplication rates, such as 300, 200 or 100, mg of Al per m². The greaterefficacy can be observed by an increased safety profile (againstnon-target organisms above and below ground (such as fish, birds andbees), improved physico-chemical properties, or increasedbiodegradability).

In each aspect and embodiment of the invention, “consisting essentially”and inflections thereof are a preferred embodiment of “comprising” andits inflections, and “consisting of” and inflections thereof are apreferred embodiment of “consisting essentially of” and its inflections.

The disclosure in the present application makes available each and everycombination of embodiments disclosed herein.

It should be noted that the disclosure herein in respect of a compoundof formula I applies equally in respect of a compound of each offormulae I*, I′a, Iaa, Iab, Iac, I′ab, Ia, Ib, Ic, Id, Ie, If, Ig, Ih,Ii, Ij, Ik, Im, In and Tables D-1 to D-66.

BIOLOGICAL EXAMPLES

The Examples which follow serve to illustrate the invention. Certaincompounds of the invention can be distinguished from known compounds byvirtue of greater efficacy at low application rates, which can beverified by the person skilled in the art using the experimentalprocedures outlined in the Examples, using lower application rates ifnecessary, for example 50 ppm, 24 ppm, 12.5 ppm, δ ppm, 3 ppm, 1.5 ppm,0.8 ppm or 0.2 ppm.

Example B1: Diabrotica Balteata (Corn Root Worm)

Maize sprouts placed onto an agar layer in 24-well microtiter plateswere treated with aqueous test solutions prepared from 10′000 ppm DMSOstock solutions by spraying. After drying, the plates were infested withL2 larvae (6 to 10 per well). The samples were assessed for mortalityand growth inhibition in comparison to untreated samples 4 days afterinfestation.

The following compounds gave an effect of at least 80% control in atleast one of the two categories (mortality or growth inhibition) at anapplication rate of 200 ppm: P.1, P.4, P.5, P.6, P.7, P.8, P.9, P.10,P.11, P.12, P.13, P.14, P.15, P.16, P.17, P.18, P.19, P.20, P.21, P.22,P.23, P.24, P.25, P.26, P.27, P.28, P.29, P.30, P.31, P.32, P.33, P.34,P.35, P.36, P.37, P.38, P.39, P.40, P.43, P.44, P.47, P.52, P.54, P.55,P.56, P.57, P.58, P.64, P.66, P.67, P.68, P.71, P.72, P.73, P.75, P.76,P.77, P.78, P.80, P.81, P.82, P.83, P.84, P.85, P.86, P.87, P.88, P.89,P.90, P.91, P.92, P.93, P.94, P.95, P.96, P.97, P.98, P.99, P.100,P.101, P.102, P.103, P.104, P.105, P.106, P.107, P.108, P.109, P.110,P.111, P.112, P.113, P.114, P.115, P.116, P.117, P.118, P.119, P.120,P.122, P.123, P.124, P.126, P.127, P.128, P.129, P.130, P.131, P.132,P.133, P.159, P.161, P.162, P.163, P.166, P.168, P.169, P.171, P.172,P.173, P.174, P.175, P.176, P.177, P.178, P.179, P.180, P.181, P.182,P.183, P.184, P.185, P.186, P.187, P.188, P.189, P.190, P.191, P.192,P.193, P.194, P.196, P.201, P.202, P.203, P.205, P.206, P.207, P.208,P.209, P.210, P.211, P.213, P.214, P.215, P.216, P.217, P.218, P.219,P.220, P.221, P.224, P.225, P.226, P.227, P.228, P.229, P.230, P.232,P.234, P.235, P.236, P.237, P.238, P.239, P.240, P.241, P.243, P.244,P.245, P.247, P.248, P.249, P.250, P.251, P.252, P.253, P.254, P.255,P.256, P.257, P.258, P.259, P.260, P.261, P.262, P.263, P.264, P.265,P.266, P.268, P.271, P.272, P.273, P.274, P.276.

Example B2: Euschistus heros (Neotropical Brown Stink Bug)

Soybean leaves on agar in 24-well microtiter plates were sprayed withaqueous test solutions prepared from 10′000 ppm DMSO stock solutions.After drying the leaves were infested with N2 nymphs. The samples wereassessed for mortality and growth inhibition in comparison to untreatedsamples 5 days after infestation.

The following compounds gave an effect of at least 80% control in atleast one of the two categories (mortality or growth inhibition) at anapplication rate of 200 ppm: P.1, P.6, P.7, P.8, P.10, P.16, P.21, P.23,P.26, P.27, P.28, P.36, P.40, P.43, P.47, P.54, P.58, P.71, P.75, P.78,P.82, P.83, P.84, P.86, P.87, P.89, P.90, P.93, P.95, P.106, P.107,P.128, P.168, P.169, P.172, P.175, P.187, P.188, P.190, P.191, P.201,P.202, P.203, P.213, P.215, P.216, P.219, P.220, P.221, P.227, P.228,P.245, P.248, P.259, P.260, P.261, P.262, P.263, P.264, P.265, P.266,P.271, P.272, P.276.

Example B3: Chilo suppressalis (Striped Rice Stemborer)

24-well microtiter plates with artificial diet were treated with aqueoustest solutions prepared from 10′000 ppm DMSO stock solutions bypipetting. After drying, the plates were infested with L2 larvae (6-8per well). The samples were assessed for mortality, anti-feeding effect,and growth inhibition in comparison to untreated samples 6 days afterinfestation. Control of Chilo suppressalis by a test sample is givenwhen at least one of the categories mortality, anti-feedant effect, andgrowth inhibition is higher than the untreated sample.

The following compounds resulted in at least 80% control in at least oneof the three categories (mortality, anti-feedant effect, or growthinhibition) at an application rate of 200 ppm: P.1, P.4, P.5, P.6, P.7,P.8, P.9, P.10, P.11, P.12, P.13, P.14, P.15, P.16, P.17, P.18, P.19,P.20, P.21, P.22, P.23, P.24, P.25, P.26, P.27, P.28, P.29, P.30, P.31,P.32, P.33, P.34, P.35, P.37, P.38, P.39, P.40, P.41, P.42, P.43, P.44,P.45, P.47, P.48, P.51, P.52, P.53, P.54, P.56, P.57, P.58, P.60, P.61,P.62, P.63, P.64, P.65, P.66, P.67, P.68, P.71, P.72, P.73, P.75, P.76,P.77, P.78, P.80, P.81, P.82, P.83, P.84, P.85, P.86, P.87, P.88, P.89,P.90, P.91, P.92, P.93, P.94, P.95, P.96, P.97, P.98, P.99, P.100,P.101, P.102, P.103, P.104, P.105, P.106, P.107, P.108, P.109, P.110,P.111, P.112, P.113, P.114, P.115, P.116, P.117, P.118, P.119, P.120,P.121, P.122, P.123, P.124, P.126, P.127, P.128, P.129, P.130, P.131,P.132, P.133, P.158, P.159, P.161, P.162, P.163, P.167, P.168, P.169,P.170, P.171, P.172, P.173, P.174, P.175, P.176, P.177, P.178, P.179,P.180, P.183, P.184, P.185, P.186, P.187, P.188, P.189, P.190, P.191,P.192, P.193, P.194, P.195, P.198, P.201, P.202, P.203, P.205, P.206,P.207, P.208, P.209, P.211, P.213, P.214, P.215, P.216, P.217, P.218,P.219, P.220, P.221, P.224, P.225, P.226, P.227, P.228, P.229, P.230,P.232, P.235, P.236, P.237, P.238, P.239, P.240, P.241, P.243, P.244,P.245, P.246, P.247, P.248, P.249, P.250, P.251, P.252, P.253, P.254,P.255, P.256, P.257, P.258, P.259, P.260, P.261, P.262, P.263, P.264,P.265, P.266, P.267, P.271, P.272, P.273, P.274, P.275, P.276.

Example B4: Plutella xylostella (Diamond Back Moth)

24-well microtiter plates with artificial diet were treated with aqueoustest solutions prepared from 10′000 ppm DMSO stock solutions bypipetting. After drying, Plutella eggs were pipetted through a plasticstencil onto a gel blotting paper and the plate was closed with it. Thesamples were assessed for mortality and growth inhibition in comparisonto untreated samples 8 days after infestation.

The following compounds gave an effect of at least 80% control in atleast one of the two categories (mortality or growth inhibition) at anapplication rate of 200 ppm: P.1, P.4, P.5, P.6, P.7, P.8, P.9, P.10,P.11, P.12, P.13, P.14, P.15, P.16, P.17, P.18, P.19, P.20, P.21, P.22,P.23, P.24, P.26, P.27, P.28, P.29, P.30, P.31, P.32, P.33, P.34, P.35,P.37, P.38, P.39, P.40, P.41, P.42, P.43, P.44, P.45, P.47, P.52, P.53,P.54, P.56, P.57, P.58, P.60, P.61, P.62, P.63, P.64, P.65, P.66, P.67,P.68, P.71, P.72, P.73, P.75, P.76, P.77, P.78, P.80, P.81, P.82, P.83,P.84, P.85, P.86, P.87, P.88, P.89, P.90, P.91, P.92, P.93, P.94, P.95,P.96, P.97, P.98, P.99, P.100, P.101, P.102, P.103, P.104, P.105, P.106,P.107, P.108, P.109, P.110, P.111, P.112, P.113, P.114, P.115, P.116,P.117, P.118, P.119, P.120, P.122, P.123, P.124, P.125, P.126, P.127,P.128, P.129, P.130, P.131, P.132, P.133, P.158, P.159, P.161, P.162,P.163, P.167, P.168, P.169, P.170, P.171, P.172, P.173, P.174, P.175,P.176, P.177, P.178, P.179, P.180, P.181, P.182, P.183, P.184, P.185,P.186, P.187, P.188, P.189, P.190, P.191, P.192, P.193, P.194, P.198,P.201, P.202, P.203, P.204, P.205, P.206, P.207, P.208, P.209, P.210,P.211, P.213, P.214, P.215, P.216, P.217, P.218, P.219, P.220, P.221,P.224, P.225, P.226, P.227, P.228, P.229, P.230, P.232, P.233, P.234,P.235, P.236, P.237, P.238, P.239, P.240, P.241, P.243, P.244, P.245,P.246, P.247, P.248, P.249, P.250, P.251, P.252, P.253, P.254, P.255,P.256, P.257, P.258, P.259, P.260, P.261, P.262, P.263, P.264, P.265,P.266, P.268, P.271, P.272, P.273, P.274, P.276.

Example B5: Myzus persicae (Green Peach Aphid) Feeding/Contact Activity

Sunflower leaf discs were placed onto agar in a 24-well microtiter plateand sprayed with aqueous test solutions prepared from 10′000 ppm DMSOstock solutions. After drying, the leaf discs were infested with anaphid population of mixed ages. The samples were assessed for mortality6 days after infestation.

The following compounds resulted in at least 80% mortality at anapplication rate of 200 ppm: P.1, P.6, P.20, P.21, P.23, P.24, P.26,P.27, P.28, P.52, P.54, P.59, P.86, P.90, P.94, P.95, P.127, P.128,P.130, P.165, P.168, P.172, P.184, P.187, P.188, P.190, P.191, P.201,P.203, P.215, P.217, P.219, P.221, P.227, P.228, P.236, P.245, P.248,P.258, P.264, P.265, P.271.

Example B6: Myzus persicae (Green Peach Aphid) Intrinsic Activity

Test compounds prepared from 10′000 ppm DMSO stock solutions wereapplied by pipette into 24-well microtiter plates and mixed with sucrosesolution. The plates were closed with a stretched Parafilm. A plasticstencil with 24 holes was placed onto the plate and infested peaseedlings were placed directly on the Parafilm. The infested plate wasclosed with a gel blotting paper and another plastic stencil and thenturned upside down. The samples were assessed for mortality 5 days afterinfestation.

The following compounds resulted in at least 80% mortality at a testrate of 12 ppm: P.1, P.6, P.10, P.11, P.12, P.16, P.18, P.20, P.21,P.22, P.23, P.24, P.26, P.27, P.28, P.29, P.32, P.40, P.44, P.52, P.54,P.58, P.66, P.71, P.82, P.84, P.86, P.87, P.88, P.90, P.91, P.93, P.94,P.95, P.98, P.127, P.128, P.130, P.132, P.133, P.162, P.168, P.169,P.171, P.172, P.177, P.182, P.183, P.184, P.187, P.188, P.190, P.191,P.194, P.201, P.202, P.203, P.208, P.215, P.217, P.219, P.220, P.221,P.227, P.228, P.229, P.230, P.236, P.243, P.245, P.248, P.258, P.260,P.262, P.263, P.264, P.265, P.266, P.271, P.272.

Example B7: Spodoptera littoralis (Egyptian Cotton Leaf Worm)

Cotton leaf discs were placed onto agar in 24-well microtiter plates andsprayed with aqueous test solutions prepared from 10′000 ppm DMSO stocksolutions. After drying the leaf discs were infested with five L1larvae. The samples were assessed for mortality, anti-feeding effect,and growth inhibition in comparison to untreated samples 3 days afterinfestation. Control of Spodoptera littoralis by a test sample is givenwhen at least one of the categories mortality, anti-feedant effect, andgrowth inhibition is higher than the untreated sample.

The following compounds resulted in at least 80% control in at least oneof the three categories (mortality, anti-feedant effect, or growthinhibition) at an application rate of 200 ppm: P.1, P.4, P.5, P.6, P.7,P.8, P.9, P.10, P.11, P.12, P.13, P.14, P.15, P.16, P.17, P.18, P.19,P.20, P.21, P.22, P.23, P.24, P.25, P.26, P.27, P.28, P.29, P.30, P.31,P.32, P.33, P.34, P.35, P.37, P.38, P.39, P.40, P.41, P.42, P.44, P.45,P.47, P.52, P.53, P.54, P.56, P.57, P.58, P.61, P.63, P.64, P.67, P.68,P.93, P.95, P.96, P.97, P.98, P.99, P.100, P.101, P.102, P.103, P.104,P.105, P.106, P.107, P.108, P.109, P.110, P.111, P.112, P.113, P.114,P.115, P.116, P.117, P.118, P.119, P.120, P.121, P.122, P.123, P.124,P.125, P.126, P.127, P.128, P.129, P.130, P.131, P.132, P.133, P.159,P.161, P.162, P.163, P.166, P.168, P.169, P.171, P.172, P.173, P.174,P.176, P.177, P.178, P.182, P.183, P.185, P.189, P.192, P.194, P.195,P.201, P.202, P.203, P.204, P.205, P.206, P.207, P.208, P.209, P.211,P.213, P.214, P.215, P.216, P.217, P.218, P.219, P.220, P.221, P.224,P.227, P.228, P.229, P.230, P.232, P.234, P.235, P.236, P.237, P.238,P.239, P.240, P.241, P.243, P.244, P.245, P.246, P.247, P.248, P.249,P.250, P.251, P.252, P.253, P.254, P.255, P.256, P.257, P.258, P.259,P.260, P.261, P.262, P.263, P.264, P.265, P.266, P.271, P.272, P.273,P.274, P.275, P.276.

Example B8: Spodoptera littoralis (Egyptian Cotton Leaf Worm)

Test compounds were applied by pipette from 10′000 ppm DMSO stocksolutions into 24-well plates and mixed with agar. Lettuce seeds wereplaced onto the agar and the multi well plate was closed by anotherplate which contained also agar. After 7 days the compound was absorbedby the roots and the lettuce grew into the lid plate. The lettuce leaveswere then cut off into the lid plate. Spodoptera eggs were pipettedthrough a plastic stencil onto a humid gel blotting paper and the lidplate was closed with it. The samples were assessed for mortality,anti-feedant effect and growth inhibition in comparison to untreatedsamples 6 days after infestation.

The following compounds gave an effect of at least 80% control in atleast one of the three categories (mortality, anti-feeding, or growthinhibition) at a test rate of 12.5 ppm: P.58, P.93, P.94, P.95, P.130,P.254, P.256.

Example B9: Plutella xylostella (Diamondback Moth)

96-well microtiter plates containing artificial diet were treated withaqueous test solutions, prepared from 10′000 ppm DMSO stock solutions,by a liquid handling robot. After drying, eggs (˜30 per well) wereinfested onto a netted lid which was suspended above the diet. The eggshatch and L1 larvae move down to the diet. The samples were assessed formortality 9 days after infestation.

The following compounds resulted in at least 80% control in mortality atan application rate of 500 ppm: P.52, P.55, P.58, P.60, P.61, P.62,P.63, P.64, P.65, P.66, P.67, P.68, P.69, P.93, P.94, P.95, P.277.

1. A compound of the formula I

wherein: A₁, A₂ and A₃ are, independently from each other, N or CR_(Y);A₄ and A₅ are, independently from each other, N or CR_(Y); Q is

R₁ is hydrogen, C₁-C₆alkyl, C₁-C₆cyanoalkyl, aminocarbonylC₁-C₆alkyl,hydroxycarbonylC₁-C₆alkyl, C₁-C₆nitroalkyl, trimethylsilaneC₁-C₆alkyl,C₁-C₃alkoxy-C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl,C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₄cycloalkylC₁-C₂alkyl-,C₃-C₄cycloalkylC₁-C₂alkyl- wherein the C₃-C₄cycloalkyl group issubstituted with 1 or 2 halogen atoms, oxetan-3-yl-CH₂—,C₁-C₆alkylcarbonyl, C₁-C₆alkoxycarbonyl, phenyloxycarbonyl,benzyloxycarbonyl, benzyl or benzyl substituted with 1 to 3 substituentsindependently selected from halogen, C₁-C₆alkoxy and C₁-C₆haloalkyl;R_(2a) and R_(2b) are each independently selected from hydrogen,C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃haloalkylsulfanyl, C₁-C₃alkoxy,C₁-C₃haloalkoxy, halogen, NO₂, SF₅, CN, C(O)NH₂, C(O)OH, C(S)NH₂,C₃-C₆cycloalkyl, C₃-C₆cycloalkyl substituted with one to threesubstituents independently selected from R_(x), C₃-C₆cycloalkylcarbonyl,phenyl, phenyl substituted with one to three substituents independentlyselected from R_(x), heteroaryl, heteroaryl substituted with one tothree substituents independently selected from R_(x); OR₆,piperidin-2-one-1-yl, piperidin-2-one-1-yl substituted with one to twosubstituents independently selected from R_(x), pyridin-2-one-1-yl,pyridin-2-one-1-yl substituted with one to two substituentsindependently selected from R_(x), azetidin-1-yl, azetidin-1-ylsubstituted with one to two substituents independently selected fromR_(x) pyrrolidin-1-yl, pyrrolidin-1-yl substituted with one to twosubstituents independently selected from R_(x),C₃-C₆cycloalkylC₁-C₄alkyl, C₃-C₆cycloalkylC₁-C₄alkyl substituted withone to two substituents independently selected from R_(z);C₃-C₆cycloalkylC₁-C₃alkoxy, C₃-C₆cycloalkylC₁-C₃alkoxy substituted withone to two substituents independently selected from R_(x),C₁-C₅cyanoalkyl, C₁-C₅cyanoalkoxy, C₁-C₄alkylsulfanyl,C₁-C₄alkylsulfanyl substituted with one to three substituentsindependently selected from R_(x), C₁-C₄alkylsulfonyl,C₁-C₄alkylsulfonyl substituted with one to three substituentsindependently selected from R_(x), C₁-C₄alkylsulfinyl, andC₁-C₄alkylsulfinyl substituted with one to three substituentsindependently selected from R_(x); R₃ is C₁-C₃alkyl or C₁-C₃haloalkyl;R₄ is pyridine, pyrimidine, pyrazine or pyridazine; or R₄ is pyridine,pyrimidine, pyrazine or pyridazine each of which, independently of eachother, is substituted with one to two substituents independentlyselected from C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₃-C₄cycloalkyl,halo, hydroxyl, CN, C₁-C₆haloalkoxy, C₂-C₆haloalkenyloxy,C₂-C₆haloalkynyloxy, C₃-C₄halocycloalkoxy. NH₂C(O)—, NH₂C(S)—,(OH)N═C(NH₂)— and a 5-membered heteroaryl ring optionally substituted by1 to 3 substituents independently selected from halogen, C₁-C₃alkyl,C₁-C₃haloalkyl, C₁-C₃alkoxy and C₁-C₃haloalkoxy; R_(4a) is pyridine,pyrimidine, pyrazine, pyridazine; or R_(4a) is pyridine, pyrimidine,pyrazine or pyridazine each of which, independently of each other, issubstituted with one to three substituents independently selected fromC₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₃-C₄cycloalkyl, halogen,hydroxyl, cyano, and C₁-C₃haloalkoxy; or R_(4a) is Y1, Y2, Y3, and Y4

wherein, R′_(4a), R′_(4b), and R′_(4c), independently of each other andindependently of Y1 to Y4, are selected from hydrogen, halogen, CN,C₁-C₃alkyl, C₁-C₃haloalkyl, C₃-C₄cycloalkyl, C₁-C₃alkoxy, andC₁-C₃haloalkoxy; R₅ is hydrogen, C₁-C₃alkyl, C₁-C₃haloalkyl,C₃-C₄cycloalkyl, C₁-C₃alkoxy, C₃-C₄alkoxyC(O)—, (C₁-C₃alkoxy)₂CH—,halogen, CN, NH₂C(O), amino (i.e NH₂), (C₁-C₃alkyl)amino,di(C₁-C₃alkyl)amino, hydroxy, C₃-C₄halocycloalkyl, C₃-C₄cyanocycloalkyl,C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl,C₁-C₄haloalkylsulfanyl, C₁-C₄haloalkylsulfinyl, C₁-C₄haloalkylsulfonyl,C₁-C₄alkylsulfanyl, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl,C₁-C₃alkoxy-C₁-C₃alkyl, C₁-C₃alkoxy-C₁-C₃alkoxy-C₁-C₃alkyl,(C₁-C₃alkyl)sulfonylamino, (C₁-C₃alkyl)sulfonyl(C₁-C₃alkyl)amino,(C₁-C₃alkyl)NHC(O), (C₁-C₃alkyl)₂NC(O), (C₁-C₃cycloalkyl)NHC(O),(C₁-C₃cycloalkyl)(C₁-C₃alkyl)NC(O), (C₁-C₃alkyl)C(O)(C₁-C₃alkyl)N,(C₁-C₃alkyl)C(O)NH, (C₁-C₃alkyl)C(O), (C₁-C₃alkoxy)C(O), HC(O),diphenylmethanimine, C₁-C₃haloalkoxy, phenyl, or a 5-memberedheteroaromatic ring; or R₅ is phenyl substituted with one to threesubstituents selected from C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,C₃-C₄cycloalkyl, halogen, CN and hydroxyl; or R₅ is a 5-memberedheteroaromatic ring substituted with one to three substituents selectedfrom C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₃-C₄cycloalkyl, halogen,CN and hydroxyl; R_(5a) and R_(5b) are, independently of each other,selected from hydrogen, halogen, CN, C₁-C₃alkyl, C₁-C₃haloalkyl,C₃-C₄cycloalkyl, C₁-C₃alkoxy, and C₁-C₃haloalkoxy; R₆ is phenyl, benzyl,heteroaryl, or C₃-C₆ cycloalkyl; or R₆ is phenyl, benzyl, heteroaryl, orC₃-C₆ cycloalkyl, each of which, independent of each other, issubstituted with one to three substituents independently selected fromR_(x); R_(x) is independently selected from halogen, C₁-C₃alkyl,C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, NO₂, SF₅, CN, C(O)NH₂,C(S)NH₂, C₁-C₄haloalkylsulfanyl, C₁-C₄haloalkylsulfinyl,C₁-C₄haloalkylsulfonyl, C₁-C₄alkylsulfanyl, C₁-C₄alkylsulfinyl andC₁-C₄alkylsulfonyl; R_(Y) is selected from hydrogen, C₁-C₃ alkyl, C₁-C₃haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, halogen, CN and cyclopropyl;and R_(Z) is selected from oxo, halogen, C₁-C₃ alkyl, C₁-C₃haloalkyl,C₁-C₃alkoxy, C₁-C₃haloalkoxy and CN; or an agrochemically acceptablesalt, stereoisomer, enantiomer, tautomer and N-oxide of the compound offormula I.
 2. The compound according to claim 1 wherein A₁ and, A₃ are Nand A₂ is CH, and A₄ is CRY and A₅ is CH.
 3. The compound according toclaim 1 wherein R¹ is hydrogen, methyl, ethyl, cyanomethyl,methoxymethyl, cyclopropyl-methyl, allyl, propargyl, benzyloxycarbonyl,or benzyl.
 4. The compound according to claim 1 wherein R_(2a) ishalogen, C₁-C₃haloalkyl, C₁-C₃haloalkylsulfanyl, C₁-C₃haloalkoxy,C₃-C₆cycloalkyl, C₃-C₆cycloalkyl substituted with one or twosubstituents independently selected from C₁-C₃haloalkyl, cyano, andhalogen, C₃-C₆cycloalkylC₁-C₄alkyl, C₃-C₆cycloalkylC₁-C₄alkylsubstituted with one to three substituents independently selected fromC₁-C₃haloalkyl, cyano, and halogen, C₁-C₅cyanoalkyl, C₁-C₄alkylsulfonyl,C₁-C₄haloalkylsulfonyl, C₁-C₄alkylsulfinyl, C₁-C₄haloalkylsulfinyl,C₃-C₆cycloalkylsulfanyl, C₃-C₆cycloalkylsulfinyl, orC₃-C₆cycloalkylsulfonyl.
 5. The compound according to claim 1 whereinR_(2b) is halogen, C₁-C₃haloalkyl, C₁-C₃haloalkylsulfanyl,C₁-C₃haloalkylsulfonyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, or CN.
 6. Thecompound according to claim 1 wherein R₃ is C₁-C₃alkyl orC₁-C₃haloalkyl.
 7. The compound according to claim 1 wherein Q is Q^(a),and R₄ is pyridine, or pyrimidine; wherein the pyridine or pyrimidine,independently of each other, is optionally substituted with onesubstituent selected from C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,C₃-C₄cycloalkyl, halo, hydroxyl, CN, C₁-C₆haloalkoxy,C₂-C₆haloalkenyloxy, C₂-C₆haloalkynyloxy, C₃-C₄halocycloalkoxy, andC₃-C₆cycloalkylC₁-C₄haloalkoxy; and R₅ is hydrogen, methyl,trifluoromethoxy, methoxy, cyclopropyl, 2,2-difluoroethoxy,2,2,2-trifluoroethoxy, difluoromethoxy, 2,2,2-trifluoroethyl, chloro,bromo, methoxyethoxy, methylcarbonyl, or methoxycarbonyl.
 8. Thecompound according to claim 1 wherein Q is Q^(b), and R_(4a) ispyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine,pyrimidine, pyrazine or pyridazine, independent of each other, isoptionally substituted with one substituent selected fromC₁-C₃haloalkyl, C₃-C₄cycloalkyl, halogen, cyano, C₁-C₃haloalkoxy andselected from Y-1 to Y-4; R_(5a) is hydrogen, halogen, CN, C₁-C₃alkyl,C₁-C₃haloalkyl, C₃-C₄cycloalkyl, C₁-C₃alkoxy or C₁-C₃haloalkoxy; R_(5b)is hydrogen, halogen, CN, C₁-C₃haloalkyl, C₃-C₄cycloalkyl, C₁-C₃alkoxy,or C₁-C₃haloalkoxy; and R_(4a), R′_(4a) and R′_(4c) independently ofeach other, are hydrogen, halogen, CN, C₁-C₃alkyl, C₁-C₃haloalkyl,C₃-C₄cycloalkyl, C₁-C₃alkoxy, and C₁-C₃haloalkoxy.
 9. The compoundaccording to claim 1 wherein the formula I is represented by

wherein R₁, R_(2a), R_(2b), R₃ are as defined in claim 1, and Q₁ isselected from Q^(aa) to Q^(ag) and Q^(ba) to Q^(bf).
 10. A compositioncomprising a compound as defined in claim 1, one or more auxiliaries anddiluent, and optionally one or more other active ingredient.
 11. Amethod (i) of combating and controlling insects, acarines, nematodes ormolluscs which comprises applying to a pest, to a locus of a pest, or toa plant susceptible to attack by a pest an insecticidally, acaricidally,nematicidally or molluscicidally effective amount of a compound asdefined in claim 1; or (ii) for the protection of plant propagationmaterial from the attack by insects, acarines, nematodes or molluscs,which comprises treating the propagation material or the site, where thepropagation material is planted, with an effective amount of a compoundas defined in claim 1; or (iii) of controlling parasites in or on ananimal in need thereof comprising administering an effective amount of acompound as defined in claim
 1. 12. A plant propagation material, suchas a seed, comprising, or treated with or adhered thereto, a compound asdefined in claim
 1. 13. A compound of the formula XI(i)

wherein A₁, A₂, A₃, A₄, A₅, R₁, R_(2a), R_(2b) and R₃ are as defined inclaim
 1. 14. A compound of the formula XIV(i)

wherein A₁, A₂, A₃, A₄, A₅, R₁, R_(2a), R_(2b) and R₃ are as defined inclaim
 1. 15. A compound of the formula II(i)

wherein A₁, A₂, A₃, A₄, A₅, R_(2a), and R_(2b) are as defined in claim1; and X1 is a halogen, such as Cl or Br.
 16. A method (i) of combatingand controlling insects, acarines, nematodes or molluscs which comprisesapplying to a pest, to a locus of a pest, or to a plant susceptible toattack by a pest an insecticidally, acaricidally, nematicidally ormolluscicidally effective amount of a composition as defined in claim10; or (ii) for the protection of plant propagation material from theattack by insects, acarines, nematodes or molluscs, which comprisestreating the propagation material or the site, where the propagationmaterial is planted, with an effective amount of a composition asdefined in claim 10; or (iii) of controlling parasites in or on ananimal in need thereof comprising administering an effective amount of acomposition as defined in claim
 10. 17. A plant propagation material,such as a seed, comprising, or treated with or adhered thereto, acomposition as defined in claim
 10. 18. A compound of the formula IV(i)

wherein A₁, A₂, A₃, A₄, A₅, R_(2a), and R_(2b) are as defined in claim1.